rho GTP-Binding Proteins
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
MAP Kinase Signaling System
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
Calcium-Calmodulin-Dependent Protein Kinases
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.
Protein Kinase C
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
p38 Mitogen-Activated Protein Kinases
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
Cyclic AMP-Dependent Protein Kinases
A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.
Mitogen-Activated Protein Kinase 1
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinase Kinases
A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.
Mitogen-Activated Protein Kinase 3
A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.
MAP Kinase Kinase Kinases
CDC2 Protein Kinase
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.
A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.
Casein Kinase II
A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.
Ribosomal Protein S6 Kinases
A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
MAP Kinase Kinase 1
Receptor Protein-Tyrosine Kinases
Extracellular Signal-Regulated MAP Kinases
A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.
MAP Kinase Kinase 4
Phosphotransferases (Alcohol Group Acceptor)
Mitogen-Activated Protein Kinases
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
I-kappa B Kinase
Glycogen Synthase Kinase 3
A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.
Protein Kinase C-alpha
Protein Kinase C-delta
Intracellular Signaling Peptides and Proteins
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
rhoA GTP-Binding Protein
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
AMP-Activated Protein Kinases
Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.
Focal Adhesion Kinase 1
A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.
An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.
Proto-Oncogene Proteins c-akt
Focal Adhesion Protein-Tyrosine Kinases
Janus Kinase 2
A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.
Amino Acid Sequence
Ribosomal Protein S6 Kinases, 90-kDa
A family of ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN.
Protein Kinase C-epsilon
A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.
MAP Kinase Kinase Kinase 1
Protein Structure, Tertiary
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Calcium-Calmodulin-Dependent Protein Kinase Type 2
A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.
Recombinant Fusion Proteins
cdc42 GTP-Binding Protein
Protein Kinase C beta
PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.
MAP Kinase Kinase 2
Cyclic GMP-Dependent Protein Kinases
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Cyclin-Dependent Kinase 2
Cell Cycle Proteins
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
TOR Serine-Threonine Kinases
A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.
Cyclin-Dependent Kinase 5
Sequence Homology, Amino Acid
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Tumor Cells, Cultured
MAP Kinase Kinase 6
Focal Adhesion Kinase 2
Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.
Mitogen-Activated Protein Kinase 8
Casein Kinase I
A casein kinase that was originally described as a monomeric enzyme with a molecular weight of 30-40 kDa. Several ISOENZYMES of casein kinase I have been found which are encoded by separate genes. Many of the casein kinase I isoenzymes have been shown to play distinctive roles in intracellular SIGNAL TRANSDUCTION.
3-Phosphoinositide-Dependent Protein Kinases
MAP Kinase Kinase 3
Aurora Kinase A
Gene Expression Regulation, Enzymologic
rac GTP-Binding Proteins
Dose-Response Relationship, Drug
Gene Expression Regulation
rac1 GTP-Binding Protein
A rac GTP-binding protein involved in regulating actin filaments at the plasma membrane. It controls the development of filopodia and lamellipodia in cells and thereby influences cellular motility and adhesion. It is also involved in activation of NADPH OXIDASE. This enzyme was formerly listed as EC 184.108.40.206.
An enzyme that is found in mitochondria and in the soluble cytoplasm of cells. It catalyzes reversible reactions of a nucleoside triphosphate, e.g., ATP, with a nucleoside diphosphate, e.g., UDP, to form ADP and UTP. Many nucleoside diphosphates can act as acceptor, while many ribo- and deoxyribonucleoside triphosphates can act as donor. EC 220.127.116.11.
Ribosomal Protein S6 Kinases, 70-kDa
A family of ribosomal protein S6 kinases that are considered the major physiological kinases for RIBOSOMAL PROTEIN S6. Unlike RIBOSOMAL PROTEIN S6 KINASES, 90KDa the proteins in this family are sensitive to the inhibitory effects of RAPAMYCIN and contain a single kinase domain. They are referred to as 70kDa proteins, however ALTERNATIVE SPLICING of mRNAs for proteins in this class also results in 85kDa variants being formed.
Elongation Factor 2 Kinase
A monomeric calcium-calmodulin-dependent protein kinase subtype that specifically phosphorylates PEPTIDE ELONGATION FACTOR 2. The enzyme lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE, however it is regulated by phosphorylation by PROTEIN KINASE A and through intramolecular autophosphorylation.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
MAP Kinase Kinase 7
Rho Guanine Nucleotide Exchange Factors
RNA, Small Interfering
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
Adaptor Proteins, Signal Transducing
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
Aurora Kinase B
Cyclin-Dependent Kinase 4
Janus Kinase 1
Cyclin-Dependent Kinase Inhibitor p27
A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.
A Kinase Anchor Proteins
A structurally-diverse family of intracellular-signaling adaptor proteins that selectively tether specific protein kinase A subtypes to distinct subcellular sites. They play a role in focusing the PROTEIN KINASE A activity toward relevant substrates. Over fifty members of this family exist, most of which bind specifically to regulatory subunits of CYCLIC AMP-DEPENDENT PROTEIN KINASE TYPE II such as CAMP PROTEIN KINASE RIIALPHA or CAMP PROTEIN KINASE RIIBETA.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
MAP Kinase Kinase Kinase 5
rhoB GTP-Binding Protein
Receptor, Epidermal Growth Factor
A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.
Glycogen Synthase Kinases
A class of protein-serine-threonine kinases that was originally found as one of the three types of kinases that phosphorylate GLYCOGEN SYNTHASE. Glycogen synthase kinases along with CA(2+)-CALMODULIN DEPENDENT PROTEIN KINASES and CYCLIC AMP-DEPENDENT PROTEIN KINASES regulate glycogen synthase activity.
Mitogen-Activated Protein Kinase 9
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
An enzyme that catalyzes reversibly the phosphorylation of deoxycytidine with the formation of a nucleoside diphosphate and deoxycytidine monophosphate. Cytosine arabinoside can also act as an acceptor. All natural nucleoside triphosphates, except deoxycytidine triphosphate, can act as donors. The enzyme is induced by some viruses, particularly the herpes simplex virus (HERPESVIRUS HOMINIS). EC 18.104.22.168.
Janus Kinase 3
A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS. The TYK2 kinase is considered the founding member of the janus kinase family and was initially discovered as a signaling partner for the INTERFERON ALPHA-BETA RECEPTOR. The kinase has since been shown to signal from several INTERLEUKIN RECEPTORS.
rho Guanine Nucleotide Dissociation Inhibitor alpha
Checkpoint Kinase 2
Toxic proteins produced from the species CLOSTRIDIUM BOTULINUM. The toxins are synthesized as a single peptide chain which is processed into a mature protein consisting of a heavy chain and light chain joined via a disulfide bond. The botulinum toxin light chain is a zinc-dependent protease which is released from the heavy chain upon ENDOCYTOSIS into PRESYNAPTIC NERVE ENDINGS. Once inside the cell the botulinum toxin light chain cleaves specific SNARE proteins which are essential for secretion of ACETYLCHOLINE by SYNAPTIC VESICLES. This inhibition of acetylcholine release results in muscular PARALYSIS.
Saccharomyces cerevisiae Proteins
Electrophoresis, Polyacrylamide Gel
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
This enzyme is a lymphoid-specific src family tyrosine kinase that is critical for T-cell development and activation. Lck is associated with the cytoplasmic domains of CD4, CD8 and the beta-chain of the IL-2 receptor, and is thought to be involved in the earliest steps of TCR-mediated T-cell activation.
Epidermal Growth Factor
A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.
rho-Specific Guanine Nucleotide Dissociation Inhibitors
Death-Associated Protein Kinases
Proto-Oncogene Proteins pp60(c-src)
Membrane-associated tyrosine-specific kinases encoded by the c-src genes. They have an important role in cellular growth control. Truncation of carboxy-terminal residues in pp60(c-src) leads to PP60(V-SRC) which has the ability to transform cells. This kinase pp60 c-src should not be confused with csk, also known as c-src kinase.
src Homology Domains
Regions of AMINO ACID SEQUENCE similarity in the SRC-FAMILY TYROSINE KINASES that fold into specific functional tertiary structures. The SH1 domain is a CATALYTIC DOMAIN. SH2 and SH3 domains are protein interaction domains. SH2 usually binds PHOSPHOTYROSINE-containing proteins and SH3 interacts with CYTOSKELETAL PROTEINS.
Transformation mediated by RhoA requires activity of ROCK kinases. (1/2130)BACKGROUND: The Ras-related GTPase RhoA controls signalling processes required for cytoskeletal reorganisation, transcriptional regulation, and transformation. The ability of RhoA mutants to transform cells correlates not with transcription but with their ability to bind ROCK-I, an effector kinase involved in cytoskeletal reorganisation. We used a recently developed specific ROCK inhibitor, Y-27632, and ROCK truncation mutants to investigate the role of ROCK kinases in transcriptional activation and transformation. RESULTS: In NIH3T3 cells, Y-27632 did not prevent the activation of serum response factor, transcription of c-fos or cell cycle re-entry following serum stimulation. Repeated treatment of NIH3T3 cells with Y-27632, however, substantially disrupted their actin fibre network but did not affect their growth rate. Y-27632 blocked focus formation by RhoA and its guanine-nucleotide exchange factors Dbl and mNET1. It did not affect the growth rate of cells transformed by Dbl and mNET1, but restored normal growth control at confluence and prevented their growth in soft agar. Y-27632 also significantly inhibited focus formation by Ras, but had no effect on the establishment or maintenance of transformation by Src. Furthermore, it significantly inhibited anchorage-independent growth of two out of four colorectal tumour cell lines. Consistent with these data, a truncated ROCK derivative exhibited weak ability to cooperate with activated Raf in focus formation assays. CONCLUSIONS: ROCK signalling is required for both the establishment and maintenance of transformation by constitutive activation of RhoA, and contributes to the Ras-transformed phenotype. These observations provide a potential explanation for the requirement for Rho in Ras-mediated transformation. Moreover, the inhibition of ROCK kinases may be of therapeutic use. (+info)
Activation of G12/G13 results in shape change and Rho/Rho-kinase-mediated myosin light chain phosphorylation in mouse platelets. (2/2130)Platelets respond to various stimuli with rapid changes in shape followed by aggregation and secretion of their granule contents. Platelets lacking the alpha-subunit of the heterotrimeric G protein Gq do not aggregate and degranulate but still undergo shape change after activation through thromboxane-A2 (TXA2) or thrombin receptors. In contrast to thrombin, the TXA2 mimetic U46619 led to the selective activation of G12 and G13 in Galphaq-deficient platelets indicating that these G proteins mediate TXA2 receptor-induced shape change. TXA2 receptor-mediated activation of G12/G13 resulted in tyrosine phosphorylation of pp72(syk) and stimulation of pp60(c-src) as well as in phosphorylation of myosin light chain (MLC) in Galphaq-deficient platelets. Both MLC phosphorylation and shape change induced through G12/G13 in the absence of Galphaq were inhibited by the C3 exoenzyme from Clostridium botulinum, by the Rho-kinase inhibitor Y-27632 and by cAMP-analogue Sp-5,6-DCl-cBIMPS. These data indicate that G12/G13 couple receptors to tyrosine kinases as well as to the Rho/Rho-kinase-mediated regulation of MLC phosphorylation. We provide evidence that G12/G13-mediated Rho/Rho-kinase-dependent regulation of MLC phosphorylation participates in receptor-induced platelet shape change. (+info)
Role of Rho and Rho kinase in the activation of volume-regulated anion channels in bovine endothelial cells. (3/2130)1. We have studied the modulation of volume-regulated anion channels (VRACs) by the small GTPase Rho and by one of its targets, Rho kinase, in calf pulmonary artery endothelial (CPAE) cells. 2. RT-PCR and immunoblot analysis showed that both RhoA and Rho kinase are expressed in CPAE cells. 3. ICl,swell, the chloride current through VRACs, was activated by challenging CPAE cells with a 25 % hypotonic extracellular solution (HTS) or by intracellular perfusion with a pipette solution containing 100 microM GTPgammaS. 4. Pretreatment of CPAE cells with the Clostridium C2IN-C3 fusion toxin, which inactivates Rho by ADP ribosylation, significantly impaired the activation of ICl,swell in response to the HTS. The current density at +100 mV was 49 +/- 13 pA pF-1 (n = 17) in pretreated cells compared with 172 +/- 17 pA pF-1 (n = 21) in control cells. 5. The volume-independent activation of ICl,swell by intracellular perfusion with GTPgammaS was also impaired in C2IN-C3-pretreated cells (31 +/- 7 pA pF-1, n = 11) compared with non-treated cells (132 +/- 21 pA pF-1, n = 15). 6. Activation of ICl,swell was pertussis toxin (PTX) insensitive. 7. Y-27632, a blocker of Rho kinase, inhibited ICl,swell and delayed its activation. 8. Inhibition of Rho and of Rho kinase by the above-described treatments did not affect the extent of cell swelling in response to HTS. 9. These experiments provide strong evidence that the Rho-Rho kinase pathway is involved in the VRAC activation cascade. (+info)
Rho-kinase in human neutrophils: a role in signalling for myosin light chain phosphorylation and cell migration. (4/2130)The role of a Rho-associated coiled-coil forming kinase in migration of neutrophils has been investigated. Rho-associated coiled-coil forming kinase I was expressed in human neutrophils. Chemotactic peptide led to a Rho-associated coiled-coil forming kinase-dependent increase in phosphorylation of myosin light chain. This was determined with the help of an antibody directed against serine 19-phosphorylated myosin light chain and an inhibitor of Rho-associated coiled-coil forming kinase (Y-27632). Y-27632 suppressed myosin light chain phosphorylation and chemotactic peptide-induced development of cell polarity and locomotion with similar potency (ED50 0.5-1.1 microM). The data strongly suggest that a Rho-associated coiled-coil forming kinase isoform, activated in human neutrophils exposed to chemotactic peptide, is important for motile functions of these cells. (+info)
Inhibition of myosin light chain kinase by p21-activated kinase. (5/2130)p21-activated kinases (PAKs) are implicated in the cytoskeletal changes induced by the Rho family of guanosine triphosphatases. Cytoskeletal dynamics are primarily modulated by interactions of actin and myosin II that are regulated by myosin light chain kinase (MLCK)-mediated phosphorylation of the regulatory myosin light chain (MLC). p21-activated kinase 1 (PAK1) phosphorylates MLCK, resulting in decreased MLCK activity. MLCK activity and MLC phosphorylation were decreased, and cell spreading was inhibited in baby hamster kidney-21 and HeLa cells expressing constitutively active PAK1. These data indicate that MLCK is a target for PAKs and that PAKs may regulate cytoskeletal dynamics by decreasing MLCK activity and MLC phosphorylation. (+info)
Distinct roles for the small GTPases Cdc42 and Rho in endothelial responses to shear stress. (6/2130)Shear stress, the tangential component of hemodynamic forces, plays an important role in endothelial remodeling. In this study, we investigated the role of Rho family GTPases Cdc42 and Rho in shear stress-induced signal transduction and cytoskeleton reorganization. Our results showed that shear stress induced the translocation of Cdc42 and Rho from cytosol to membrane. Although both Cdc42 and Rho were involved in the shear stress-induced transcription factor AP-1 acting on the 12-O-tetradecanoyl-13-phorbol-acetate-responsive element (TRE), only Cdc42 was sufficient to activate AP-1/TRE. Dominant-negative mutants of Cdc42 and Rho, as well as recombinant C3 exoenzyme, attenuated the shear stress activation of c-Jun NH2-terminal kinases (JNKs), suggesting that Cdc42 and Rho regulate the shear stress induction of AP-1/TRE activity through JNKs. Shear stress-induced cell alignment and stress fiber formation were inhibited by the dominant-negative mutants of Rho and p160ROCK, but not by the dominant-negative mutant of Cdc42, indicating that the Rho-p160ROCK pathway regulates the cytoskeletal reorganization in response to shear stress. (+info)
The Caenorhabditis elegans mel-11 myosin phosphatase regulatory subunit affects tissue contraction in the somatic gonad and the embryonic epidermis and genetically interacts with the Rac signaling pathway. (7/2130)Caenorhabditis elegans embryonic elongation is driven by cell shape changes that cause a contraction of the epidermal cell layer enclosing the embryo. We have previously shown that this process requires a Rho-associated kinase (LET-502) and is opposed by the activity of a myosin phosphatase regulatory subunit (MEL-11). We now extend our characterization and show that mel-11 activity is required both in the epidermis during embryonic elongation and in the spermatheca of the adult somatic gonad. let-502 and mel-11 reporter gene constructs show reciprocal expression patterns in the embryonic epidermis and the spermatheca, and mutations of the two genes have opposite effects in these two tissues. These results are consistent with let-502 and mel-11 mediating tissue contraction and relaxation, respectively. We also find that mel-11 embryonic inviability is genetically enhanced by mutations in a Rac signaling pathway, suggesting that Rac potentiates or acts in parallel with the activity of the myosin phosphatase complex. Since Rho has been implicated in promoting cellular contraction, our results support a mechanism by which epithelial morphogenesis is regulated by the counteracting activities of Rho and Rac. (+info)
Phosphorylation of adducin by Rho-kinase plays a crucial role in cell motility. (8/2130)Adducin is a membrane skeletal protein that binds to actin filaments (F-actin) and thereby promotes the association of spectrin with F-actin to form a spectrin-actin meshwork beneath plasma membranes such as ruffling membranes. Rho-associated kinase (Rho- kinase), which is activated by the small guanosine triphosphatase Rho, phosphorylates alpha-adducin and thereby enhances the F-actin-binding activity of alpha-adducin in vitro. Here we identified the sites of phosphorylation of alpha-adducin by Rho-kinase as Thr445 and Thr480. We prepared antibody that specifically recognized alpha-adducin phosphorylated at Thr445, and found by use of this antibody that Rho-kinase phosphorylated alpha-adducin at Thr445 in COS7 cells in a Rho-dependent manner. Phosphorylated alpha-adducin accumulated in the membrane ruffling area of Madin-Darby canine kidney (MDCK) epithelial cells and the leading edge of scattering cells during the action of tetradecanoylphorbol-13-acetate (TPA) or hepatocyte growth factor (HGF). The microinjection of Botulinum C3 ADP-ribosyl-transferase, dominant negative Rho-kinase, or alpha-adducinT445A,T480A (substitution of Thr445 and Thr480 by Ala) inhibited the TPA-induced membrane ruffling in MDCK cells and wound-induced migration in NRK49F cells. alpha-AdducinT445D,T480D (substitution of Thr445 and Thr480 by Asp), but not alpha-adducinT445A,T480A, counteracted the inhibitory effect of the dominant negative Rho-kinase on the TPA-induced membrane ruffling in MDCK cells. Taken together, these results indicate that Rho-kinase phosphorylates alpha-adducin downstream of Rho in vivo, and that the phosphorylation of adducin by Rho-kinase plays a crucial role in the regulation of membrane ruffling and cell motility. (+info)
ROCK inhibitors for the treatment of ocular diseases<...
TY - JOUR. T1 - ROCK inhibitors for the treatment of ocular diseases. AU - Nourinia, Ramin. AU - nakao, shintaro. AU - Zandi, Souska. AU - Safi, Sare. AU - Hafezi-Moghadam, Ali. AU - Ahmadieh, Hamid. PY - 2018/1/1. Y1 - 2018/1/1. N2 - The Rho-kinase/ROCK (Rho-associated coiled-coil-containing protein kinase) pathway is involved in the pathogenesis of multiple ocular and systemic disorders. Recently, ROCK inhibitors have been suggested as novel treatments for various ocular diseases. Several in vitro, in vivo and clinical studies have demonstrated the safety and efficacy of ROCK inhibitors in the management of ocular disorders such as corneal epithelial and endothelial damage, glaucoma, retinal and choroidal neovascularisation, diabetic macular oedema and optic nerve disorders. In this review, these studies are explored with focus on the relevant clinical investigations.. AB - The Rho-kinase/ROCK (Rho-associated coiled-coil-containing protein kinase) pathway is involved in the pathogenesis of ...
WD repeat and coiled-coil-containing protein elisa and antibody
Shop WD repeat and coiled-coil-containing protein ELISA Kit, Recombinant Protein and WD repeat and coiled-coil-containing protein Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.
Roles of Rho-associated Kinase in Cytokinesis; Mutations in Rho-associated Kinase Phosphorylation Sites Impair Cytokinetic...
Roles of Rho-associated Kinase in Cytokinesis; Mutations in Rho-associated Kinase Phosphorylation Sites Impair Cytokinetic Segregation of Glial ...
Transgene regulation system responding to Rho associated coiled-coil kinase (ROCK) activation<...
TY - JOUR. T1 - Transgene regulation system responding to Rho associated coiled-coil kinase (ROCK) activation. AU - Tsuchiya, Akira. AU - Kang, Jeong Hun. AU - Asai, Daisuke. AU - Mori, Takeshi. AU - Niidome, Takuro. AU - Katayama, Yoshiki. N1 - Funding Information: This work was financially supported by a grant-in-aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture in Japan and also supported by A3 Foresight Program in Japan Society for the Promotion of Science . A. T. is grateful to Japan Society for the Promotion of Science (JSPS) for the DC scholarship. PY - 2011/10/10. Y1 - 2011/10/10. N2 - Recently, we have proposed a new system of gene regulation called drug or gene delivery system responding to cellular signals (D-RECS). In this system, transgene expression is activated in response to intracellular target protein kinases or proteases for safe, cell-specific gene delivery by using peptide-polymer conjugates. Here we applied this system to an ...
Rho-kinase activation in endothelial cells contributes to expansion of infarction after focal cerebral ischemia | Read by QxMD
Microcirculatory disturbances contribute to the expansion of infarct lesions after focal cerebral ischemia. Recently, it was shown that Rho-kinase involves in endothelial dysfunction via down-regulation of endothelial nitric oxide synthase function in a rodent stroke model. However, it is not clear whether endothelial Rho-kinase is activated in vivo or Rho-kinase activation contributes to microcirculatory disturbances after cerebral ischemia. In this study, we assessed the temporal and spatial profiles of Rho-kianse activity and the effect of the Rho-kinase inhibitor fasudil on microcirculatory disturbances in the focal brain ischemia. Rho-kinase activation was evaluated by analyzing the phosphorylation of adducin, a substrate of Rho-kinase, by immunohistochemistry. Staining for p-adducin was found in endothelia in the ischemic area 6 hr after induction of ischemia. Microcirculatory disturbances and increased endothelial cell staining for von Willebrand factor (vWF) were observed in the same ...
CiNii 論文 - Molecular Mechanisms and Therapeutic Strategies of Chronic Renal Injury :...
Among the GTP-binding proteins, Rho is known to function as a molecular switch in various cellular functions. Among the Rho effectors, the cellular function and signal transduction of Rho-kinase have been extensively studied. However, information about its in vivo functions is still limited. With the recent development of a specific Rho-kinase inhibitor such as Y-27632 and fasudil, the understanding of the role of the Rho/Rho-kinase pathway in vitro and in vivo has advanced. However, to date, there have been few studies investigating the role of Rho-kinase in renal disease. Recent studies have shown that Rho-kinase inhibitor significantly attenuated the tubulointerstitial fibrosis in kidney induced by unilateral ureteral obstruction. However, there have been few studies investigating the role of the Rho/Rho-kinase pathway in hypertensive glomerular sclerosis. In this review, we described the role of the Rho/Rho-kinase pathway in the progression of renal glomerulosclerosis in several forms of ...
Microparticles harboring Sonic Hedgehog promote angiogenesis through the up-regulation of adhesion proteins and pro-angiogenic...
Microparticles (MPs) are small fragments generated from the plasma membrane after cell stimulation or apoptosis. We have recently shown that MPs harboring the morphogen Sonic Hedgehog (MPsShh1) correct endothelial injury by release of nitric oxide from endothelial cells [Agouni, Mostefai, Porro, Carusio, Favre, Richard, Henrion, Martı´nez and Andriantsitohaina (2007) FASEB J., 21, 2735-2741]. Here, we show that MPsShh1 induce the formation of capillary-like structures in an in vitro model using human endothelial cells, although they inhibited cell migration. Besides, MPsShh1 regulate cell proliferation. Both cell adhesion and expression of proteins involved in this process such as Rho A and phosphorylation of focal-activated kinase were increased by MPsShh1, via a Rho-associated coiled-coil-containing protein kinase inhibitor-sensitive pathway. We demonstrate that MPsShh1 increase messenger RNA and protein levels of proangiogenic factors as measured by quantitative reverse transcription- ...
Rho Kinase Inhibitors: Potential Treatments for Diabetes and Diabetic Complications | Bentham Science
Title:Rho Kinase Inhibitors: Potential Treatments for Diabetes and Diabetic Complications. VOLUME: 18 ISSUE: 20. Author(s):Hong Zhou and Yong-jun Li. Affiliation:Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.. Keywords:RhoA, Rho kinase, inhibitors, diabetes, complications, GTPase, hypertension, coronary vasospasm, stroke, atherosclerosis. Abstract:The small GTPase RhoA and its downstream effector, Rho kinase (ROCK), appear to mediate numerous pathophysiological signals, including smooth muscle cell contraction, actin cytoskeleton organization, cell adhesion and motility, proliferation, differentiation and the expression of several genes. Clinical interest in the RhoA/ROCK pathway has increased, due to emerging evidence that this signaling pathway is involved in the pathogenesis of several diseases, including hypertension, coronary vasospasm, stroke, atherosclerosis, heart failure and diabetes; ROCK is considered an important future ...
Defective endothelial nitric oxide synthase signaling is mediated by rho-kinase activation in rats with secondary biliary...
The current study demonstrates that in secondary biliary cirrhosis (1) Rho-kinase activation is substantially involved in the defective eNOS signaling; (2) Rho-kinase may directly interact with Akt and subsequently inhibit Akt-eNOS signaling; and (3) the intravenous infusion of a regular dose of fasudil (1 mg/kg/hour), a specific inhibitor of Rho-kinase, significantly decreases PVP without reducing HTBF through the up-regulation of eNOS.. Liver cirrhosis is associated with increased intrahepatic vascular resistance leading to portal hypertension. HSC contractility, which is regulated by the balance between vasoconstricting agents such as endothelin-1 and vasorelaxing agents such as NO, contributes to increased intrahepatic vascular resistance. HSCs are also a major source of extracellular matrix in liver cirrhosis, and their activation increases hepatic fibrosis, resulting in increased intrahepatic vascular resistance. Rho-kinase, a downstream effector of GTPase Rho, has been shown to be ...
Endothelial repair in stented arteries is accelerated by inhibition of Rho-associated protein kinase. - Sheffield Hallam...
Aims: Stent deployment causes endothelial cell (EC) denudation, which promotes in-stent restenosis and thrombosis. Thus endothelial regrowth in stented arteries is an important therapeutic goal. Stent struts modify local hemodynamics, however the effects of flow pertubation on EC injury and repair are incompletely understood. By studying the effects of stent struts on flow and EC migration we identified an intervention that promotes endothelial repair in stented arteries. Methods and Results: In vitro and in vivo models were developed to monitor endothelialization under flow and the influence of stent struts. A 2D parallel-plate flow chamber with 100 μm ridges arranged perpendicular to the flow was used. Live cell imaging coupled to computational fluid dynamic simulations revealed that EC migrate in the direction of flow upstream from the ridges but subsequently accumulate downstream from ridges at sites of bidirectional flow. The mechanism of EC trapping by bidirectional flow involved reduced ...
Rho-associated protein kinase 2 (IPR029878) | InterPro | EMBL-EBI
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
ROCK Targeted Library | Kinase Sharp-aimed Targeted Libraries | Targeted and Focused Screening Libraries | Life Chemicals
Rho-associated protein kinases (ROCK) are serine/threonine kinases involved in numerous cellular motility regulation processes from cell migration to cellular contractility and control of the amount of microfilaments.. ROCK1 and ROCK2 isoforms have been used as targets in virtual screening performed by Life Chemicals with Schrödinger software that has also been used for preparation of protein molecule conformations. Both ROCK kinase structures (PDB IDs: 2ESM and 4L6Q) were optimized with protein preparation tool. At the same time, a number of known ROCK1 and ROCK2 inhibitors with IC50 lower than 1.5 µM from ChEMBL were processed with LigPrep module to generate 3D conformers with different pH states (Epik). Further, all docking procedures were carried out with Glide (Fig. 1). Several H-bond constraints and hydrophobic regions were defined and were applied during the docking stage. Based on docking score values, the docked compounds from Life Chemicals Stock Collection were narrowed down ...
2013 November | SRC Signaling
The addition of both MEK1 inhibitor U0126 or JNK inhibitor SP600125 coupled with RI inhibitor SB431542 had no detectable result to the mesenchymal phenotype on the cells. The mixture these details of p38 MAPK inhibitor SB203580 and ROCK inhibitor Y27632 restored cortical actin stain ing, but tension fiber actin remained inside the cells. Escalating the concentration of RI inhibitor SB431542 to ten M led to a even more lessen from the level of anxiety fib ers, nonetheless, the combination of RI inhibitor SB431542 by using a p38 MAPK inhibitor SB203580 or ROCK inhibitor Y27632 was additional effective at getting rid of them. Related results were observed in wild variety mTEC cells, which has a mixture of RI inhibi tor SB431542 and ROCK inhibitor Y27632 reversing EMT as indicated by each gene expression and cell morphology. Collectively, these information indicate that therapy in the cells with RI inhibitor SB431542 by itself are unable to result in total re acqui selleck AZD4547 sition of cortical ...
The therapeutic effects of Rho-ROCK inhibitors on CNS disorders | TCRM
The therapeutic effects of Rho-ROCK inhibitors on CNS disorders Takekazu Kubo1, Atsushi Yamaguchi1, Nobuyoshi Iwata2, Toshihide Yamashita1,31Department of Neurobiology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan; 2Information Institute for Medical Research Ltd.; 3Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University 2-2 Yamadaoka, Suita, Osaka 565-0871, JapanAbstract: Rho-kinase (ROCK) is a serine/threonine kinase and one of the major downstream effectors of the small GTPase Rho. The Rho-ROCK pathway is involved in many aspects of neuronal functions including neurite outgrowth and retraction. The Rho-ROCK pathway becomes an attractive target for the development of drugs for treating central nervous system (CNS) disorders, since it has been recently revealed that this pathway is closely related to the pathogenesis of several CNS disorders such as spinal cord injuries, stroke, and Alzheimer’s disease (AD). In the adult
Rho Kinase Inhibition Is Essential During In Vitro Neurogenesis and Promotes Phenotypic Rescue of Human Induced Pluripotent...
Compagnucci, C, et al. (2016) Rho Kinase Inhibition Is Essential During In Vitro Neurogenesis and Promotes Phenotypic Rescue of Human Induced Pluripotent Stem Cell-Derived Neurons With Oligophrenin-1 Loss of Function. Stem Cells Transl Med. 2016 Jul 1; 5(7):860-9. PM ID: ...
Adhesion strength has influence on ROCK activity and va | Open-i
Adhesion strength has influence on ROCK activity and various cell activities in a dose dependent manner.A. To compare the relative levels of ROCK activation, de
Cancer Stem Cells and Radioresistance: Rho/ROCK Pathway Plea Attention
Stem Cells International is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies in all areas of stem cell biology and applications. The journal will consider basic, translational, and clinical research, including animal models and clinical trials.
Results for cd05621
Catalytic domain of the Protein Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 2. Serine/Threonine Kinases (STKs), ROCK subfamily, ROCK2 (or ROK-alpha) isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ROCK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. ROCK2 was the first identified target of activated RhoA, and was found to play a role in stress ...
Editing 1 mutant mice to demonstrate that the MYPT1 phosphorylation at T696, but - Tourism Wiki
Even so in airway smooth muscle, each the knockout or inhibition of Pak reduces tone (Hoover et al., 2012), and Pak3 has been shown to induce a Ca2+independent contraction of permeabilized smooth muscle (Van Eyk et al., 1998; [https://www.medchemexpress.com/Maribavir.html MedChemExpress GW257406X] McFawn et al., 2003).In addition, Pak also has been demonstrated to phosphorylate CPI-17 (Takizawa et al., 2002). Constant with this hypothesis are the outcomes demonstrating that in SHR compared with control rats, each the [https://www.medchemexpress.com/ly-411575.html LY-411575 site] sensitivity to G-protein-coupled agonists as well as the magnitude and sensitivity of Ca2+ sensitization are improved (Satoh et al., 1994) at the same time as research defining the function of G12-G13induced activation of Rho kinase-mediated Ca2+ sensitization for the improvement of DOCA salt-sensitive hypertension (Wirth et al., 2008). Additionally, the infusion in the Rho kinase inhibitor Y-27632 lowered blood pressure ...
ROCK | 抑制剂 激动剂 拮抗剂 调节剂 | MCE
ROCK (Rho-associated protein kinase) is a kinase belonging to the AGC (PKA/ PKG/PKC) family of serine-threonine kinases. ROCKs (ROCK1 and ROCK2) occur in mammals, zebrafish, Xenopus, invertebrates and chicken. Human ROCK1 has a molecular mass of 158 kDa and is a major downstream effector of the small GTPase RhoA. Mammalian ROCK consists of a kinase domain, acoiled-coil region and a Pleckstrin homology (PH) domain, which reduces the kinase activity of ROCKs by an autoinhibitory intramolecular fold if RhoA-GTP is not present. ROCK plays a role in a wide range of different cellular phenomena, as ROCK is a downstream effector protein of the small GTPase Rho, which is one of the major regulators of the cytoskeleton.. ...
CCL19/21 induced PI3K-dependent phosphorylation of Akt/protein kinase B, activation of the Rho/Rho-associated coiled-coil forming protein kinases/myosin light chain pathway and MAPKs phosphorylation ...
Rho family GTPases have received increasing attention as critical regulators of cell function (1). Initially, they were shown to regulate actin dynamics, thereby modulating development, cell migration, immune responses, and cancer cell invasion and metastasis. More recent studies have shown that they are also involved in cell-cell adhesion and cell cycle progression. RhoA is one of the most widely studied of the 22 mammalian members of the family, and the serine-threonine kinase Rho kinase (ROCK) is a major RhoA effector.. RhoA/ROCK has a number of functions in the kidney. RhoA/ROCK enhances Ca2+-dependent vascular smooth muscle contraction, thereby modulating tone (2-4). The potent vasoconstrictor angiotensin II (AngII) activates ROCK in smooth muscle cells. The ROCK inhibitors fasudil and Y-27632 dilate afferent and efferent arterioles and reverse AngII-dependent arteriolar vasoconstriction. At the cellular level, RhoA/ROCK mediates cytoskeletal rearrangement in renal tubule cells, mesangial ...
Results for cd05622
Catalytic domain of the Protein Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 1. Serine/Threonine Kinases (STKs), ROCK subfamily, ROCK1 (or ROK-beta) isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ROCK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. ROCK1 is preferentially expressed in the liver, lung, spleen, testes, and kidney. It mediates ...
Rho Links Calcium, Cell Death | ALZFORUM
Excitotoxic cell death, the end for many cells after ischemic brain injury and in some neurodegenerative diseases, is triggered by glutamate-induced calcium influx. Downstream, activation of the p38α map kinase leads to apoptosis, but just how calcium and p38 connect has been an open question. New results from Michael Courtneys lab at the University of Kuopio in Finland show that the small GTPase Rho is the missing link. Their work, published in the March 18 online edition of Nature Neuroscience, establishes Rho activation by calcium influx as a necessary and sufficient event to turn on p38 and cause cell death in primary neurons.. Their results open up a potential new target for drugs to block excitotoxicity, and may have some additional relevance to Alzheimer disease. Inhibitors of Rho and its downstream kinase Rock can modulate amyloid-β (Aβ) peptide production (Zhou et al., 2003; Leuchtenberger et al., 2006). In addition, Rho is farnesylated, and changes in Rho/Rock pathway activity have ...
Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II)...
TY - JOUR. T1 - Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors. AU - Feng, Yangbo. AU - Yin, Yan. AU - Weiser, Amiee. AU - Griffin, Evelyn. AU - Cameron, Michael D.. AU - Lin, Li. AU - Ruiz, Claudia. AU - Schürer, Stephan C.. AU - Inoue, Toshihiro. AU - Rao, P. Vasanth. AU - Schröter, Thomas. AU - LoGrasso, Philip. PY - 2008/11/13. Y1 - 2008/11/13. N2 - The identification of a new class of potent and selective ROCK-II inhibitors is presented. Compound 5 (SR-3677) had an IC50 of ∼3 nM in enzyme and cell based assays and had an off-target hit rate of 1.4% against 353 kinases, and inhibited only 3 out of 70 nonkinase enzymes and receptors. Pharmacology studies showed that 5 was efficacious in both, increasing ex vivo aqueous humor outflow in porcine eyes and inhibiting myosin light chain phosphorylation.. AB - The identification of a new class of potent and selective ROCK-II inhibitors is presented. ...
RCSB PDB - Protein Feature View - Rho-associated protein kinase 1 - Q13464 (ROCK1 HUMAN)
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
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Dysbindin, or dystrobrevin-binding protein 1, is a coiled-coil-containing protein expressed in muscle and brain that was identified as a binding…
DTNB - ويكيبيديا، الموسوعة الحرة
Benson MA، Newey SE، Martin-Rendon E، وآخرون. (2001). Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain.. J. Biol. Chem. 276 (26): 24232-41. PMID 11316798. doi:10.1074/jbc.M010418200. الوسيط ...
p116Rip targets myosin phosphatase to the actin cytoskeleton a...
p116Rip targets myosin phosphatase to the actin cytoskeleton and is essential for RhoA/ROCK-regulated neuritogenesis.: Activation of the RhoA-Rho kinase (ROCK)
Rock-2 phospho Y256 Antibody 600-401-998
This antibody is designed, produced, and validated as part of a collaboration between Rockland and the National Cancer Institute (NCI) and is suitable for Cancer, Immunology and Nuclear Signaling research. Progression of tumors to invasive and metastatic forms requires that tumor cells undergo dramatic morphological changes, a process regulated by Rho GTPases. Increased levels of RhoA or RhoC, as well as the Rho effector proteins ROCK-1 or ROCK-2, were observed in various human carcinomas. In vivo studies have also shown that ROCK inhibition reduced the invasiveness of several tumor cell lines. It is suggested that Rho and ROCK signaling contribute to the morphological changes and metastatic behavior of some tumor cells. Thus, elevated Rho and ROCK expression is associated with tumorigenesis, particularly during the progression to invasive and metastatic phenotypes. Phosphorylation of certain residues in ROCK-2 may be critical for its kinase activity.
Characterization and purification of truncated human rho-kinase ii expressed in sf-21 cells
Rho-kinase II (ROCK-II) is a serine/threonine kinase that is involved in regulation of smooth muscle contraction and has been shown to contribute to the early stages of axon formation in neurons and the regulation of the neuronal cytoskeleton. Much of what is known about Rho-kinase function comes from cell-biological studies, whereas a paucity of biochemical characterization exists for the enzyme. In an effort to characterize ROCK-II biochemically we have cloned a truncated form of human ROCK-II comprising amino acids 1-543 and overexpressed it in Sf-21 cells. Utilizing the Sf-21/baculovirus expression system we isolated milligram quantities of ROCK-II (1-543) and purified the enzyme to near homogeneity. Optimal expression conditions revealed that infection of Sf-21 cells at a multiplicity of infection of 10 for 72h yielded maximal protein expression. Expression of ROCK-II (1-543) as an N-terminal Flag fusion protein allowed a single-step purification yielding greater than 90% homogeneous ...
V.A. - Maxell Rock II Sampler - Vinyl LP - 1980 - US - Original | hhv.de
V.A. - Maxell Rock II Sampler - Vinyl LP - 1980 - US - Original günstig online kaufen bei hhv.de - Versandkostenfrei bestellen ab 80€!
JoVE Author Search: Bova S
Artery, Bay, Bay K 8644, Cell, Concentration, Endothelium, Kinase, Kinases, Kinetics, Muscle, Muscle Contraction, Myocytes, Protein Kinase, Protein Kinase Inhibitors, Protein Kinases, Rat, Regulation, Rho Kinase, Rho-associated Kinase, Role
Twig Scotland - Igneous rock
Rocks that form by the cooling and solidification of magma or lava. Igneous rocks are the most common of the three types of rock on Earth, sedimentary and metamorphic rocks making up only about one-twentieth of the crust. Extrusive igneous rocks are formed when lava cools at the surface, while intrusive igneous rocks are those that cool and form underground.. ...
Gentaur Molecular :Cell Biolabs \ 96-Well ROCK Activity Assay Kit \ STA-416-5
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moontap icu - Page 35 - simple wordpress site
We offer new ways of deriving the expressions reported in our previous work for assessing the quality of pairwise models. Rotational spectroscopy of the atmospheric photo-oxidation product o-toluic acid and its monohydrate. MLC phosphorylation in MKs is regulated by Rho-associated kinase ...
Miscellaneous Compounds - Page 2 - NF-κB signaling in inflammation and cancer
The goal of this study was to define the AVL-292 AVL-292 role from the Rho category of little GTPases in the β-adrenergic regulation from the Na K-ATPase in alveolar epithelial cells (AEC). not really prevent RhoA activation by ISO. Finally the ISO-mediated Na K-ATPase exocytosis was governed with the Rho-associated kinase (Rock and roll) as […]. Read More ». ...
Disruption of K2P6.1 Produces Vascular Dysfunction and Hypertension in Mice | Hypertension
Although human, rat, and mouse K2P6.1s have been cloned and the electrophysiological properties studied in heterologous expression systems,4,5,17 the physiological function of K2P6.1 is presently not known. The fact that K2P6.1 is highly expressed in all of the blood vessels studied to date2,7-10 led us to ask questions regarding the functional role of K2P6.1 in the vascular system. Our studies reveal the following: (1) K2P6.1 influences systemic blood pressure; (2) K2P6.1 regulates the contractile state of vascular muscle, likely by setting its membrane potential and rho kinase activity; and (3) K2P6.1 does not appear to be involved with VSMC migration, proliferation, or volume regulation in the models tested.. We acknowledge the inherent limitations in the use of a mouse KO model, because pretranslational or posttranslational changes in other genes can occur with gene deletion, especially when the gene deletion leads to pathophysiological conditions, such as hypertension. Further studies into ...
MicroRNA-21 Integrates Pathogenic Signaling to Control Pulmonary HypertensionClinical Perspective | Circulation
The direct regulation of Rho/Rho-kinase by miR-21 augments our evolving understanding of this pathway in the diseased pulmonary vasculature. Upregulation of RhoA is known to induce Rho-kinase activity, leading to pulmonary vascular pathology.28 Less is known about the functions of RhoB in the vasculature, although, in cell culture, it suppresses angiogenesis41 and can induce a vasoconstrictive phenotype by activating endothelin-142 and repressing endothelial nitric oxide synthase.31 Thus, our findings emphasize the underappreciated importance of RhoB in control of the dysregulated pulmonary vessel.. Furthermore, integration of various PH-relevant stimuli by miR-21 correlates with the known pleiotropic activity of this miRNA in various pathological contexts (as reviewed in Reference 39). Although modulation of RhoB reflects an important function of miR-21, other direct targets of miR-21 may affect downstream PH development. Among these, BMPRII may represent a key target given its role in PH ...
Rushing Water On Rock Outcrop stock photo | iStock
Download this Rushing Water On Rock Outcrop photo now. And search more of the webs best library of royalty-free stock images from iStock.
Rho-Kinase - ECM & Adhesion Molecules
H 1152 dihydrochloride is a rho-kinase (ROCK) inhibitor that displays high selectivity over other protein kinases (IC50 values are 0.012, 0.180, 0.360, 0.745, 3.03, 5.68 and 28.3 μM for ROCKII, CAMKII, PKG, Aurora A, PKA, PKC and MLCK respectively). Learn More ...
Pets Megastore : DOG ROCKS! Prevents urine burn patches in your lawn.  - US$9.21 [AU$11.50] discount medical supplies for...
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Oxidative species increase arginase activity in endothelial cells through the RhoA/Rho kinase pathway<...
TY - JOUR. T1 - Oxidative species increase arginase activity in endothelial cells through the RhoA/Rho kinase pathway. AU - Chandra, S.. AU - Romero, M. J.. AU - Shatanawi, A.. AU - Alkilany, A. M.. AU - Caldwell, R. B.. AU - Caldwell, R. William. PY - 2012/1/1. Y1 - 2012/1/1. N2 - Background and Purpose NO produced by endothelial NOS is needed for normal vascular function. During diabetes, aging and hypertension, elevated levels of arginase can compete with NOS for available l-arginine, reducing NO and increasing superoxide (O 2 .-) production via NOS uncoupling. Elevated O 2 .- combines with NO to form peroxynitrite (ONOO -), further reducing NO. Oxidative species increase arginase activity, but the mechanism(s) involved are not known. Our study determined the mechanism involved in peroxynitrite and hydrogen peroxide-induced enhancement in endothelial arginase activity. We hypothesized that oxidative species increase arginase activity through PKC-activated RhoA/Rho kinase (ROCK) pathway. ...
Possible involvement of rho kinase 1 (rock 1) in cecal ligation and puncture-induced sepsis | Critical Care | Full Text
We have previously demonstrated that following cecal ligation and puncture (CLP) there is an increase in lung epithelial apoptosis in a rat model . On the other hand, it has been shown that the rho/rho kinase pathway is involved in mechanisms of several aspects such as endothelial cell dysfunction and apoptosis. However, the role of rho kinase in the concept of sepsis-induced apoptosis has yet to be elucidated. In this study, to investigate the possible contribution of rho/rho kinase signalling in CLP-induced lung injury, rho kinase expression and the possible protective effect of the administration of an inhibitor of rho kinase, (+)-(R)-trans-4-1-aminoethyl-N-4-pyridyl cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632), has been investigated in rats in this model.. Thirty-two male Wistar rats were randomly divided into four groups: (1) sham, (2) CLP, (3) sham + Y27632, (4) CLP + Y27632. Y27632 was administered at 1.5 mg/kg, intaperitoneally, 20 min before performing operations. ...
Rho-kinase signalling regulates CXC chemokine formation and leukocyte recruitment in colonic ischemiaâ€reperfusion
Leukocyte recruitment is a key feature in ischemiaâ€reperfusion (I/R)-induced tissue injury. The aim of the present study was to investigate the effect of Rho-kinase inhibition on I/R-provoked leukocyte recruitment in the colon. C57BL/6 mice were subjected to 30 min of ischemia by clamping of the superior mesenteric artery followed by 120 min of reperfusion. Intraperitoneal pretreatment with the selective Rho-kinase inhibitors fasudil (4â€40 mg/kg) and Y-27632 (1â€10 mg/kg) was administered prior to induction of colonic I/R. Leukocyteâ€endothelium interactions were analyzed by intravital fluorescence microscopy. Colonic content of tumour necrosis factor-Î± (TNF-Î±) and the CXC chemokines macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (KC) were determined by ELISA. Additionally, colonic activity of myeloperoxidase (MPO), a marker of leukocyte infiltration, and malondialdehyde (MDA), were quantified. Fasudil and Y-27632 pretreatment ...
Data Availability StatementRaw data were generated at Nara Medical School Hospital. Data Availability StatementRaw data were...
Supplementary MaterialsSupplementary_Data. affected the cell count number and the protein content levels in the bronchoalveolar lavage fluid. In addition, treatment with SPHK1 inhibitor reduced the wet-to-dry percentage of the lungs and suppressed Evans blue dye leakage into the lung cells. Furthermore, SPHK1 inhibitor exhibited protecting effects within the two-hit model of VALI by inhibiting the Ras homolog family member a-mediated phosphorylation of myosin phosphatase target subunit 1 (MYPT-1) and endothelial hyperpermeability. Additionally, mice were divided into five additional organizations: i) Non-ventilated group; ii) non-ventilated + LPS group; iii) ventilated group; iv) ventilated + LPS group; and v) ventilated + LPS + Rho-associated coiled-coil forming protein kinase (ROCK)1 inhibitor group. ROCK1 inhibitor (10 mg/kg) was injected intraperitoneally 1 h prior to air flow. The present results suggested that ROCK1 inhibitor could attenuate mechanical stretch-induced lung endothelial ...
Decreased RhoA expression in myocardium of diabetic rats<...
TY - JOUR. T1 - Decreased RhoA expression in myocardium of diabetic rats. AU - Tang, Jiping. AU - Fitzgerald, Sharyn M.. AU - Boughtman, Brandi N.. AU - Cole, Samuel W.. AU - Brands, Michael W.. AU - Zhang, John H.. PY - 2005/8/1. Y1 - 2005/8/1. N2 - Diabetic cardiomyopathy is one of the major causes of death in diabetic patients, but the pathogenesis is unclear. There is evidence that RhoA, a small GTPase, might be involved in cardiac function. This study, therefore, analyzed RhoA expression and activation in hearts of diabetic rats. Male Sprague-Dawley rats were divided into control and diabetic groups of 18 each. Diabetes was induced by intravenous injection of streptozotocin (55 mg/kg). Rats were studied 3 weeks after induction of diabetes. Heart rate, which was measured 24 h/day, decreased by 93 ± 7 beats/min in diabetic rats. There was a 62% decrease (p , 0.01) in RhoA mRNA expression in heart tissues (left ventricle) of diabetic rats (38.5 ± 6.7 × 106 molecules/μg total RNA) compared ...
Enhancement of corneal endothelium wound healing by Rho-associated kinase (ROCK) inhibitor eye drops | British Journal of...
Methods As an in vitro model, cultivated cynomolgus monkey corneal endothelial cells were scraped to create a linear defect. The wound distance was then determined during a 24-h culture in the presence or absence of 10 μM of Y-27632. As an in vivo model, central corneal endothelium of Japanese white rabbits was damaged by transcorneal freezing, then 10 mM of Y-27632 was applied topically six times daily for 48 h. The wound area of the corneal endothelium was evaluated after 48 h. ...
Lipoxin A<sub>4</sub> mediates aortic contraction via rhoa/rho kinase, endothelial dysfunction and reactive oxygen...
TY - JOUR. T1 - Lipoxin A4 mediates aortic contraction via rhoa/rho kinase, endothelial dysfunction and reactive oxygen species. AU - Wenceslau, Camilla F.. AU - Mccarthy, Cameron Grant. AU - Szasz, Theodora. AU - Webb, R. Clinton. PY - 2014/3/6. Y1 - 2014/3/6. N2 - Background: Lipoxin A4 (LXA4) is a biologically active product generated from arachidonic acid by lipoxygenase action. The production of lipoxins is enhanced by aspirin through acetylation of cyclooxygenase-2, via a mechanism known as aspirin-triggered lipoxin. LXA4 has both anti-inflammatory and proinflammatory actions, the latter being related with reocclusion and restenosis after coronary angioplasty in patients treated with aspirin. However, little is known of the actions of LXA4 on the vasculature. We hypothesized that LXA4 promotes contractile responses and contributes to endothelial dysfunction. Methods: We used aorta from Wistar rats to assess vascular function. Reactive oxygen species (ROS) production and contractile and ...
TACC2 - Wikipedia
Transforming acidic coiled-coil-containing protein 2 is a protein that in humans is encoded by the TACC2 gene. Transforming acidic coiled-coil proteins are a conserved family of centrosome- and microtubule-interacting proteins that are implicated in cancer. This gene encodes a protein that concentrates at centrosomes throughout the cell cycle. This gene lies within a chromosomal region associated with tumorigenesis. Expression of this gene is thought to affect the progression of breast tumors. Expression of this gene is also induced by erythropoietin. GRCh38: Ensembl release 89: ENSG00000138162 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000030852 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Gangisetty O, Lauffart B, Sondarva GV, Chelsea DM, Still IH (Apr 2004). The transforming acidic coiled coil proteins interact with nuclear histone acetyltransferases. Oncogene. 23 (14): 2559-63. doi:10.1038/sj.onc.1207424. PMID 14767476. Entrez Gene: TACC2 ...
Human BAT2D1 ELISA Kit | biobool.com
Protein PRRC2C ELISA KIT; BAT2 domain-containing protein 1 ELISA KIT; HBV X-transactivated gene 2 protein ELISA KIT; HBV XAg-transactivated protein 2 ELISA KIT; HLA-B-associated transcript 2-like 2 ELISA KIT; Proline-rich and coiled-coil-containing protein 2CPRRC2C ELISA KIT; BAT2D1 ELISA KIT; BAT2L2 ELISA KIT; KIAA1096 ELISA KIT; XTP2 ELISA ...
Plexin signaling hampers integrin-based adhesion, leading to Rho-kinase independent cell rounding, and inhibiting lamellipodia...
Plexins encode receptors for semaphorins, molecular signals guiding cell migration, and axon pathfinding. The mechanisms mediating plexin function are poorly understood. Plexin activation in adhering cells rapidly leads to retraction of cellular processes and cell rounding cell collapse). Here we show that, unexpectedly, this response does not require the activity of Rho-dependent kinase (ROCK) nor the contraction of F-actin cables. Interestingly, integrin-based focal adhesive structures are disassembled within minutes upon plexin activation; this is followed by actin depolymerization and, eventually, by cellular collapse. We also show that plexin activation hinders cell attachment to adhesive substrates, blocks the extension of lamellipodia, and thereby inhibits cell migration. We conclude that plexin signaling uncouples cell substrate-adhesion from cytoskeletal dynamics required for cell migration and axon extension.
Pfam: PP1 inhibitor
GF ID PP1_inhibitor #=GF AC PF05361.11 #=GF DE PKC-activated protein phosphatase-1 inhibitor #=GF AU Finn RD #=GF SE Pfam-B_69711 (release 7.8) #=GF GA 20.70 20.70; #=GF TC 20.70 20.80; #=GF NC 20.60 20.30; #=GF BM hmmbuild HMM.ann SEED.ann #=GF SM hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq #=GF TP Family #=GF RN  #=GF RM 11734001 #=GF RT Solution NMR structure of the myosin phosphatase inhibitor #=GF RT protein CPI-17 shows phosphorylation-induced conformational #=GF RT changes responsible for activation. #=GF RA Ohki S, Eto M, Kariya E, Hayano T, Hayashi Y, Yazawa M, #=GF RA Brautigan D, Kainosho M; #=GF RL J Mol Biol 2001;314:839-849. #=GF DR INTERPRO; IPR008025; #=GF DR SCOP; 1k5o; fa; #=GF CC Contractility of vascular smooth muscle depends on #=GF CC phosphorylation of myosin light chains, and is modulated by #=GF CC hormonal control of myosin phosphatase activity. Signaling #=GF CC pathways activate kinases such as PKC or Rho-dependent kinases #=GF CC that phosphorylate the ...
Protein phosphatase 1 regulatory subunit 12A (Myosin phosphatase-targeting subunit 1) (Myosin phosphatase target subunit 1) (Proteinphosphatase myosin-binding subunit ...
Rock Classification - Hicksville Public Schools / Homepage
FINAL REVIEW: ROCKS & MINERALS 1. Which statement is true of all rocks? (1) Rocks contain organic material. (2) Rocks contain fossils. (3) Rocks are composed of minerals. (4) Rocks are formed in layers. 2. Weathering and erosion of Earths crust are primarily caused by (1) gravity (3) evaporation (2) volcanic activity (4) sedimentation 3. The diagram below shows a rock sample and an identification key. Natural Cement Key Shell fragment Feldspar fragment Quartz fragment This rock sample would best be classified as (1) volcanic (3) metamorphic (2) sedimentary (4) igneous 4. Igneous rocks are formed by: (1) weathering (3) volcanic activity (2) cementation (4) sedimentation 5. If shell fragments are found in a rock sample, it is most likely that the rock formed: (1) on a mountain slope (3) on a glacier (2) from magma (4) in shallow water 6. In which type of rock are fossils generally found? (1) igneous (3) sedimentary (2) metamorphic (4) volcanic 7. Dust and ash entering the atmosphere as a result ...
Mechanism of modulation of huntingtin exon 1 aggregation by profilin | JPND
DESCRIPTION (provided by applicant): Huntingtons disease (HD) is a devastating neurodegenerative disease caused by CAG codon expansion in exon 1 of the huntingtin (htt) gene. Exon 1 spanning protein products, referred to as Httex1 are the major components of neuronal intranuclear inclusions that are the hallmarks of HD. Y-27632, a small molecule inhibitor of the rho-associated kinase (ROCK), was shown by the Diamond lab to reduce Httex1 aggregation in cells and ameliorate Httex1-mediated toxicity in Drosophila and mouse models. Serine-137 of profilin was established as the direct target of ROCK. Phospho-profilin does not reduce Httex1 aggregation whereas unphosphorylated profilin modulates Httex1 aggregation through direct interactions thus explaining the effect of Y-27632. We envisage a direct therapeutic approach that involves the design of molecules to mimic the effects of profilin. Such an approach requires a comprehensive understanding of the mechanisms by which profilin suppresses Httex1 ...
Myocardial remodeling in rats with metabolic syndrome: role of Rho-kinase mediated insulin resistance - Acta Biochimica...
Insulin resistance (IR) plays a critical role in metabolic syndrome (MS). Previous studies have demonstrated that activated ROCK is increased in MS patients. However, the effect of Rho-kinase (ROCK) on IR has not been definitely determined. Thus, the aims of the present study were to determine whether ROCK activation induces IR or affects myocardial structure and function, as well as the possible mechanisms underlying this process. Wistar rats fed high fat, high glucose and high salt diet sewed as model of MS and we used transmission electron microscopy, echocardiogram technology, and terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling staining to identify any myocardial damage. The protein levels of MYPT-1 (characteristic of ROCK activation), IRS-1 and AKT were analyzed by immunohistochemistry and Western blotting. In hearts from MS rats, we found increased protein levels of phospho-MYPT-1 and phospho-IRS-1 (Ser307) and decreased phospho-AKT compared to levels in normal rats. ...
Endothelial Nitric Oxide Synthase Inhibits G12/13 and Rho-Kinase Activated by the Angiotensin II Type-1 Receptor |...
The major novel finding of the present study is that exogenously introduced eNOS in VSMCs, with its expression relatively comparable to the endogenous level, markedly inhibited AngII-induced Rho/ROCK pathway activation, and subsequent VSMC migration via its specific inhibition on G12/13 coupled to the AT1 receptor. Overexpression of eNOS such as by adenovirus has been shown to inhibit VSMC proliferation, hypertrophy, as well as migration associated with a wide variety of inhibitions of the upstream signal transductions and gene transcriptions.40-43 However, it is still difficult to conclude whether the observations were translatable to physiological consequences of eNOS-dependent vascular protection, because most of the past studies might overexpress eNOS far beyond the eNOS amount expressed in endothelial cells. For example, marked inhibition of VSMC proliferation by eNOS adenovirus were observed between 150 to 1000 moi,40,41 whereas the inhibition of thymidine incorporation, migration, and ...
Membrane depolarization activates BK channels through ROCK-mediated β1 subunit surface trafficking to limit vasoconstriction |...
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An essential role for p120-catenin in Src- and Rac1-mediated anchorage-independent cell growth | JCB
Although high RhoA-ROCK activity clearly suppresses AIG, the evidence does not fully exclude the possibility that p120s role might be independent of Rac1 and Src signaling pathways, as is clearly the case with H-Ras. For example, Rac1 and Src might normally suppress RhoA-ROCK activity via p120-independent mechanisms that are then unable to compensate for elevated RhoA-ROCK activity caused separately by p120 ablation. It is worth noting, however, that the effects of p120 ablation are not so potent as to be insurmountable, as indicated by the data on H-Ras. Regardless of the exact mechanism, the ultimate effects of both Rac1 and Src on the RhoA-ROCK pathway and on AIG are clearly dependent on p120.. Interestingly, although H-Ras did not require p120, its ability to induce AIG nonetheless depended on suppression of the ROCK-LIMK cascade and activation of cofilin (Fig. 5). Ras has been shown previously to inhibit ROCK by at least three different cell type-specific mechanisms, including ...
Dual Roles for Rhoa/Rho-Kinase in the Regulated Trafficking of a Volta by Lee Stirling
Kv1.2 is a member of the Shaker family of voltage-sensitive potassium channels and contributes to regulation of membrane excitability. The electrophysiological activity of Kv1.2 undergoes tyrosine kinase-dependent suppression in a process involving RhoA. We report that RhoA elicits suppression of Kv1.2 ionic current by modulating channel endocytosis. This occurs through two distinct pathways, one clathrin-dependent and the other cholesterol-dependent. Activation of RhoA downstream effectors Rho-kinase (ROCK) or protein kinase N (PKN) via the lysophosphatidic acid (LPA) receptor elicits clathrin-dependent Kv1.2 endocytosis and consequent attenuation of its ionic current. LPA-induced channel endocytosis is blocked by ROCK inhibition , dominant negative PKN, or by clathrin RNAi. In contrast, steady-state endocytosis of Kv1.2 in un-stimulated cells is cholesterol-dependent. Inhibition of basal ROCK with Y27632 or basal PKN with HA1077 increases steady-state surface Kv1.2. The Y27632-induced increase
Abstract 4029: Decreased Rho Kinase (ROCK) Activity by Angiotensin Converting Enzyme Inhibitor (ACEi) is Associated With...
Background: Heart failure (HF) is associated with decreased cardiac contractility and ventricular remodeling, features which are partially reversed by angiotensin converting enzyme inhibitors (ACEi). Since Rho kinase (ROCK) mediates cellular contraction through effects on the actin cytoskeleton and is an important regulator of cardiac fibrosis, we hypothesize that ACEi may improve heart function through inhibition of ROCK activity.. Methods and Results: We enrolled 30 consecutive HF subjects (average age: 52.7±8.2, 60% male in gender, NYHA class 3.2±1.1), with impaired left ventricular ejection fraction (LVEF) of less than 40% by echocardiography (average LVEF=32.1±8.2%), and age- and sex-matched 30 subjects with preserved LVEF function (average LVEF=65.4±9.4%) as the control group. ROCK activity was determined in peripheral leukocytes using a phospho-specific antibody for myosin binding subunit (MBS). Compared with the control group, the subjects with impaired LVEF have higher ROCK activity ...
Pulldown Activation Assays to study Rho pathway, Rock pathway, ERK pathway, Ras pathway and Ral small G-protein families.
Cytoskeletons pulldown assay kits are the most comprehensive kits available, rhoA protein, rac1 GLISA, cdc42 pulldown, small g-proteins, gtpase, cell motility, pulldown, activation assay, cell shape, lamellipodia, filopodia, microspikes, focal adhesions, ras p21, h-ras, k-ras, arf1, arf6, cytoskeleton, gtpase protein, g-lisa, small g-protein assay, rho pulldown, rhoa pulldown, rho activation assay, rhoa activation assay.
JCI - Citations to mTORC1 loss impairs epidermal adhesion via TGF-β/Rho kinase activation
Despite its central position in oncogenic intracellular signaling networks, the role of mTORC1 in epithelial development has not been studied extensively in vivo. Here, we have used the epidermis as a model system to elucidate the cellular effects and signaling feedback sequelae of mTORC1 loss of function in epithelial tissue. In mice with conditional epidermal loss of the mTORC1 components Rheb or Rptor, mTORC1 loss of function unexpectedly resulted in a profound skin barrier defect with epidermal abrasions, blistering, and early postnatal lethality, due to a thinned epidermis with decreased desmosomal protein expression and incomplete biochemical differentiation. In mice with mTORC1 loss of function, we found that Rho kinase (ROCK) signaling was constitutively activated, resulting in increased cytoskeletal tension and impaired cell-cell adhesion. Inhibition or silencing of ROCK1 was sufficient to rescue keratinocyte adhesion and biochemical differentiation in these mice. mTORC1 loss of ...
Screening for cell migration inhibitors via automated microscopy reveals a Rho-kinase inhibitor
Small-molecule kinase inhibitors are predominantly discovered in pure protein assays. We have discovered an inhibitor of Rho-kinase (ROCK) through an image-based, high-throughput screen of cell monolayer wound healing. Using automated microscopy, we screened a library of approximately 16,000 compoun …
Ultrasonography, Doppler, Pulsed | Profiles RNS
Soga J, Noma K, Hata T, Hidaka T, Fujii Y, Idei N, Fujimura N, Mikami S, Maruhashi T, Kihara Y, Chayama K, Kato H, Liao JK, Higashi Y. Rho-associated kinase activity, endothelial function, and cardiovascular risk factors. Arterioscler Thromb Vasc Biol. 2011 Oct; 31(10):2353-9 ...
trans-N-(o-chlorobenzyl)-N-(cyclohexylmethyl)-1,4cyclohexanebis(methylamine) dihydrochloride | C22H37Cl3N2 - PubChem
trans-N-(o-chlorobenzyl)-N-(cyclohexylmethyl)-1,4cyclohexanebis(methylamine) dihydrochloride | C22H37Cl3N2 | CID 77088 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more.
Molecular mechanism for the regulation of rho-kinase by dimerization and its inhibition by fasudil<...
TY - JOUR. T1 - Molecular mechanism for the regulation of rho-kinase by dimerization and its inhibition by fasudil. AU - Yamaguchi, Hiroto. AU - Kasa, Miyuki. AU - Amano, Mutsuki. AU - Kaibuchi, Kozo. AU - Hakoshima, Toshio. N1 - Funding Information: We thank Y. Miwa for preparing gel filtration data and preparing the sample for the enzyme assay; J. Tsukamoto for her technical support in performing MALDI-TOF MS and the N-terminal analysis; and Drs. T. Tsukihara, A. Nakagawa, and E. Yamashita at SPring-8 for use of the synchrotron beamline 44XU. This work was supported in part by a Protein 3000 project on Signal Transduction from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (to T.H.). PY - 2006/3. Y1 - 2006/3. N2 - Rho-kinase is a key regulator of cytoskeletal events and a promising drug target in the treatment of vascular diseases and neurological disorders. Unlike other protein kinases, Rho-kinase requires both N- and C-terminal extension segments outside ...
Supplementary MaterialsSupplementary Figures - Rho-kinase inhibition research
Supplementary MaterialsSupplementary Figures. Additionally, other circRNAs can interact with RNA-binding proteins or be translated into proteins, as respectively exemplified by  and . Recent developments in the field of circRNAs have led to an increasing interest in characterizing their relevance in bountiful diseases. Specially, many studies focused on the role of circRNAs in tumor development and their biomarker potential reveal that circRNAs correlated with clinical pathological characteristics represent an attractive new class of biomarkers, such as for diagnosis, prognosis and prediction [16C19]. In spite of the emerging BC-associated circRNAs, such as  and , other circRNAs relevance and function in BC have not been thoroughly addressed and remain largely unclear. As one member of the zinc finger protein family, zinc finger with KRAB and SCAN domains 1 (in BC. According to Jeck et al.  and Salzman et al. , a covalently linked 668-nt circRNA termed is generated by ...
Rock Broke Off, Fall on Rock, Climbing Unroped, Failure to Test Holds, Inadequate Protection, Inexperience - Kentucky, Red...
ROCK BROKE OFF, FALL ON ROCK, CLIMBING UNROPED, FAILURE TO TEST HOLDS, INADEQUATE PROTECTION, INEXPERIENCE. Kentucky, Red River Gorge State Park. On October 2, a climber (22) was on top of Courthouse Rock looking for an anchor placement for rappelling. He had his harness on but was unroped. He went near the edge and the rock broke off underneath him, resulting in his fall off the cliff of about 75 feet, with an additional 25 feet of tumbling at the bottom. His partner went to get help, and three hours later, a search and rescue team arrived and brought the victim out on a rolling backboard. He suffered a pneumothorax and fractured arms.. Analysis. Rappelling is a very popular activity in this park. The victim reported that he had limited experience and was unfamiliar with the area. The sandstone in this area is unstable, but there are plenty of trees to anchor to while exploring around the top of the cliff. Many of the accidents here are the result of hikers, etc., getting drunk and falling off. ...
Adventurous Young Guy Sitting On Rock Against Blue Sky stock photo | iStock
Download this Adventurous Young Guy Sitting On Rock Against Blue Sky photo now. And search more of the webs best library of royalty-free stock images from iStock.
Snail On Rocks Throw Pillow for Sale by Steve Somerville
Snail On Rocks Throw Pillow by Steve Somerville. Our throw pillows are made from 100% spun polyester poplin fabric and add a stylish statement to any room. Pillows are available in sizes from 14 x 14 up to 26 x 26. Each pillow is printed on both sides (same image) and includes a concealed zipper and removable insert (if selected) for easy cleaning.
Tomorrowland: What the future holds in glaucoma therapies
The present method of lowering IOP as a means of preventing optic neuropathy is expanding beyond prostaglandin analogues and beta blockers to include novel therapeutics, such as Rho kinase (ROCK) inhibitors, the adenosine class of drugs, and nitric oxide added to prostaglandins, said John R. Samples, MD.
ROCK Inhibition Primes Tumor Tissue to Sensitize Cells to Chemotherapy | Cancer Discovery
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S2 Series Diffusion Sensor / Transmitter | RKI-65-2405RK, RKI-65-2405RK-05, RKI-65-2394RK-CH4, RKI-65-2395RK-CH4 | RKI...
The S2 Series Diffusion Sensor/Transmitter features water repellent sensor coating, explosion proof construction, and optional stainless steel junction box.
CRYSTALCLEAR® D-SOLV™ « aqualinewaterfeatures.com
CrystalClear® D-Solv™ is a dry crystal which utilizes the latest cutting edge technology to remove pond owners worst pond problem. D-Solv™ cleans within a short period to remove debris, add oxygen and clean the pond from top to bottom. Use CrystalClear® D-Solv™ on waterfalls, streams and rocks in and around the pond. CrystalClear® D-Solv should be applied when the rocks are wet, and then allowed to sit a minimum of 4 hours, or overnight (best). Start your pump in the morning, and the rocks are washed clean! Available in 2 lb, 10 lb and 25 lb sizes.. ...
Oil Painting Commission | Elaine dEsterre
EARLY STAGES This commission is centered on a land-form called Point Roadknight situated on the Surf Coast along the Great Ocean Road. Part of my process includes taking photographs and frottage. The photographs show the context, the environment in which the specific rocks that structure this feature of the landscape. The particular rocks are columnar…
ROCK1 Floxed Mouse | Mouse Models - Ximbio
Rho associated coiled-coil containing protein kinases (ROCKs) exist in mammals, zebrafish, Xenopus, C. elegans and Drosophila. They are mainly involved
Mineralogical comparisons of experimental results investigating the biological impacts on rock transport processes -...
This study investigates the influence of microbes on fluid transport in sedimentary and igneous host rock environments. It particularly focuses on granodiorite rock (Äspö; Sweden) and mudstone (Horonobe; Japan) that were utilised during laboratory-based column experiments. The results showed that biofilms fo
Nordling Bangs His Head On ROCK OF AGES!
Nordling here. ROCK OF AGES, for all the music, glam, and bluster, is really about one thing - one young womans journey from getting off the bus to getting on the pole. In between we get some musical numbers that range from barely karaoke...
Dynamics of RhoA and ROKα translocation in single living cells | SpringerLink
The RhoA-binding kinase (ROK) is one of the target kinases of RhoA and is known to play a critical role in regulating cytoskeletal rearrangement in cells. ROK translocates to the plasma membrane fract
Deformation And Failure of Crystalline Rock And an Elastoplastic Homogenization Theory | ISRM EUROCK | OnePetro
Mechanical properties of rock are affected by Its microstructure such as constituent minerals and microcracks. Microscopic studies of cracks in post- loaded samples were made by using a scanning electron microscope (Friedman et al. 1970; Wong 1982; Mardon et al. 1990). For damage propagation,. Peng et al. (1972) loaded Chelmsford granite specimens to various levels, unloaded, cut lengthwise into halves and then observed. These experimental studies showed that macroscopic fractures grow from grain-scale microcracks. Whereas, these works have a drawback that they were performed under zero stress condition using thin or cut section after experiment or under artificially fractured condition. We developed a new testing equipment to observe the micro-damage behavior continuously during the deformation without unloading for the same specimen. The experiments were currently carried out under uniaxial compression. The effect of microscale structure for fracturing process of rock is not simple. In this ...
UofL Libraries Digital Collections
Loading rock at Wolfe County, Kentucky. Seven young men in overalls or jeans and white shirts surround a wheelbarrow and bend to hit rocks with mallets. The rocks are fist sized and light in color. The men are surrounded by a wall of dark boulders ...
greenatopia: Walking through our geologic past
Pretty much every informative sign in Death Valley mentions how this rock formation, or that canyon, is a wonderful example of our geologic past. Meaning that because you can see the stratification so well, you can really see what has happened to the Earth (or at least in CA) recently. And when I say recently, I mean these last few hundred million years or so. Death Valleys oldest rocks are around 1.7 billion years old. Those rocks, though, dont tell much of a story since they have been altered so much over time. But the rocks from 500 million years ago do tell us something, most notable, that this was a warm, shallow sea. And the reason those rocks still tell us something is because they were only recently thrust to the surface ...
Swine Flu - Free Range Humans
Do you still think its safe to take government-recommended vaccines? What rock are you living under? This Amazing Document is now in the Public Domain This 1920 book provides absolute links to the same Rockefeller-funded vaccines which today are causing seizures in children taking gardasil shots, giving autism to children who take recommended rounds of […]. read more ...
Green and Golden Heart Design Rock
This rock has a pretty green background with golden swirls and red accents. It is a great size rock to be a paper weight for that pile of mail on your counter or hold your book open while you are eating soup. Rocks are pretty little decorations and can hang out anywhere in your home
What is the importance of rocks? | Reference.com
Rocks have a broad range of uses that makes them significantly important to human life. For instance, rocks are used in construction, for manufacturing substances and making medicine and for the...
What radioactive isotopes are used for absolute dating - Principles radiometric dating | Geochemistry and environmental.
This method works because some unstable (radioactive) isotopes of some. In these cases, usually the half-life of interest in radiometric dating is the. Two radiometric methods used for igneous rocks are uranium-lead dating and potassium-argon dating.
The origin of the oldest rocks - Tuetego
The oldest rocks found so far on Planet Earth are at the Acasta River in Canadas North-West Territories. Discovered about 30 years ago, these rocks are felsic granite, which means that they are ric
Drs. Elizabeth Martin and Padhu Pattabiraman present the Science of Disease Grand Rounds in September. During their presentation they discuss glaucoma and Rho kinase inhibitors in the clinic and in… ...
It inhibits the enzyme rho kinase. This appears to increase outflow of aqueous humor through the trabecular meshwork, and also ...
Tolias KF, Cantley LC, Carpenter CL (July 1995). "Rho family GTPases bind to phosphoinositide kinases". The Journal of ... The amino acid sequence of this enzyme does not show homology to other kinases, but the recombinant protein does exhibit kinase ... "The sequence of phosphatidylinositol-4-phosphate 5-kinase defines a novel family of lipid kinases". The Journal of Biological ... "Protein kinase C mediates translocation of type II phosphatidylinositol 5-phosphate 4-kinase required for platelet alpha- ...
Somlyo AP (1999). "Kinases, myosin phosphatase and Rho proteins: curiouser and curiouser". J. Physiol. 516 (3): 630. doi: ... Somlyo AP, Wu X, Walker LA, Somlyo AV (1999). "Pharmacomechanical coupling: the role of calcium, G-proteins, kinases and ...
1996). "Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase)". Science. 273 (5272): 245-8. Bibcode: ... Rho-associated kinase (Rho-kinase), which is activated by GTP. RhoA, phosphorylated MBS and consequently inactivated myosin ... Thus, Rho appears to inhibit myosin phosphatase through the action of Rho-kinase. PPP1R12A has been shown to interact with ... Somlyo AP (1999). "Kinases, myosin phosphatase and Rho proteins: curiouser and curiouser". J. Physiol. 516 (3): 630. doi: ...
... is a biochemical tool used in the study of the rho-associated protein kinase (ROCK) signaling pathways. Y-27632 ... Selective probe of ROCK/Rho-kinase". Jikken Igaku. 17 (7): 850-855. Uehata, M; Ishizaki, T; Satoh, H; Ono, T; Kawahara, T; ... 1997). "Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension". Nature. 389 (6654 ... "The effects of Rho-associated kinase inhibitor Y-27632 on primary human corneal endothelial cells propagated using a dual media ...
"Rho-Associated, Coiled-Coil Containing Protein Kinase 1". Hahmann C, Schroeter T (January 2010). "Rho-kinase inhibitors as ... ROCK1 is a protein serine/threonine kinase also known as rho-associated, coiled-coil-containing protein kinase 1. Other common ... Rho kinase GRCh38: Ensembl release 89: ENSG00000067900 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000024290 - ... Rath N, Olson MF (October 2012). "Rho-associated kinases in tumorigenesis: re-considering ROCK inhibition for cancer therapy". ...
p21-activated kinases (PAKs) 1, 2 and 3 via SH3 domain. c-Cbl via SH3 domain. Rho family GTP-binding protein family members ... Brown MC, West KA, Turner CE (2002). "Paxillin-dependent paxillin kinase linker and p21-activated kinase localization to focal ... Rho guanine nucleotide exchange factor 7 is a protein that in humans is encoded by the ARHGEF7 gene. ARHGEF7 is commonly known ... Manser E, Loo TH, Koh CG, Zhao ZS, Chen XQ, Tan L, Tan I, Leung T, Lim L (July 1998). "PAK kinases are directly coupled to the ...
2000). "Phosphorylation of collapsin response mediator protein-2 by Rho-kinase. Evidence for two separate signaling pathways ...
... including increased Rho-kinase activity. Increased levels of Rho-kinase inhibit myosin phosphatase activity, leading to ... which phosphorylates and inhibits GTPase RhoA and decreases Rho-kinase activity. Reduced Rho-kinase activity permits an ... Rho-kinase also decreases nitric oxide synthase activity, which reduces nitric oxide concentrations. Lower levels of nitric ... Takemoto, M; Sun, J; Hiroki, J; Shimokawa, H; Liao, JK (Jul 2, 2002). "Rho-kinase mediates hypoxia-induced downregulation of ...
Hickson GR, Echard A, O'Farrell PH (February 2006). "Rho-kinase controls cell shape changes during cytokinesis". Current ... which is required for the function of metaphase cyclin-dependent kinases (M-Cdks). In essence, Activation of the Anaphase- ...
Rho kinase inhibitor Patel RA, Forinash KD, Pireddu R, Sun Y, Sun N, Martin MP, et al. (October 2012). "RKI-1447 is a potent ... RKI-1447 is a drug which acts as a potent and selective inhibitor of the enzyme Rho kinase, with an IC50 of 14.5 nM at ROCK1 ... Dang Y, Wang C, Shah P, Waxman S, Loewen RT, Loewen NA (January 2019). "RKI-1447, a Rho kinase inhibitor, causes ocular ... December 2019). "Inhibition of Rho-Associated Kinase Suppresses Medulloblastoma Growth". Cancers. 12 (1): 73. doi:10.3390/ ...
Nagumo H, Sasaki Y, Ono Y, Okamoto H, Seto M, Takuwa Y (Jan 2000). "Rho kinase inhibitor HA-1077 prevents Rho-mediated myosin ... Fasudil (INN) is a potent Rho-kinase inhibitor and vasodilator. Since it was discovered, it has been used for the treatment of ... Fasudil (HA-1077) is a selective RhoA/Rho kinase (ROCK) inhibitor. ROCK is an enzyme that plays an important role in mediating ... Ocaranza MP, Rivera P, Novoa U, Pinto M, González L, Chiong M, Lavandero S, Jalil JE (Apr 2011). "Rho kinase inhibition ...
... which activates Rho-kinase (this one generates GTP) and it finally leads to increased smooth muscle cell migration and division ... with other signaling pathway like RhoA/Rho-kinase signaling. A malfunction can therefore lead to different diseases (see ... "AAMP Regulates Endothelial Cell Migration and Angiogenesis Through RhoA/Rho Kinase Signaling". Annals of Biomedical Engineering ...
"Diaphonous-related fromins bridge Rho GTP-ase and Src tyrosine kinase signaling". Mol. Cell. 5 (1): 13-25. doi:10.1016/S1097- ... Rho-GTP binds to the GDB domain and disrupts the DAD-DID-interaction thus promoting actin assembly. But this requires high ... The N terminus consists of a Rho GTPase-binding domain (GBD), which is joint to the formin homology 3 (FH3). DAD can mediate ... in 1997 as a downstream effector of Rho. A mouse embryo cDNA library was screened to identify a RhoA-GTP-binding protein using ...
Rho associated coiled-coil containing protein kinase 2 is a protein that in humans is encoded by the ROCK2 gene. Fasudil is an ... "Entrez Gene: Rho associated coiled-coil containing protein kinase 2". Retrieved 2016-04-21. CS1 maint: discouraged parameter ( ... Overview of all the structural information available in the PDB for UniProt: O75116 (Human Rho-associated protein kinase 2 ( ... link) Trauger JW, Lin FF, Turner MS, Stephens J, LoGrasso PV (2002). "Kinetic mechanism for human Rho-Kinase II (ROCK-II)". ...
Transforming protein RhoA
Due to pathophysiological overlap of RhoA and Rho-kinase in asthma, both RhoA and Rho-kinase have become promising new target ... Fauré J, Dagher MC (May 2001). "Interactions between Rho GTPases and Rho GDP dissociation inhibitor (Rho-GDI)". Biochimie. 83 ( ... RhoA and Rho kinase mechanisms have been linked to diabetes due to the up-regulated expression of targets within type 1 and 2 ... Among them, ROCK1 (Rho-associated, coiled-coil containing protein kinase 1) and DIAPH1 (Diaphanous Homologue 1, a.k.a. hDia1, ...
ARHGAP31: Rho GRPase activating protein 31. *C3orf1: chromosome 3 open reading frame 1 ... PIK3CA: phosphoinositide-3-kinase, catalytic, alpha polypeptide. *PROSER1: Proline and serine rich protein 1 ...
Other kinases that have interested Sebti include Rho-associated kinase and Aurora kinase. STAT3. In 2003 the Sebti lab ... October 1, 2012). "RKI-1447 is a potent inhibitor of the Rho-associated ROCK kinases with anti-invasive and antitumor ... Kinases. Sebti's work on the kinase Akt led to his interest in Triciribine. ... The Sebti lab has particularly focused on the role of the Ras superfamily, including the Ras and Rho subfamilies and the Ral ...
Induced stem cells
Kurosawa, H. (2012). "Application of Rho-associated protein kinase (ROCK) inhibitor to human pluripotent stem cells". Journal ... A cocktail of small molecules, Y-27632, A-83-01 (a TGFβ kinase/activin receptor like kinase (ALK5) inhibitor), and CHIR99021 ( ... Schlegel and Liu demonstrated that the combination of feeder cells and a Rho kinase inhibitor (Y-27632) induces normal and ... "Efficient Procurement of Epithelial Stem Cells from Human Tissue Specimens Using a Rho-Associated Protein Kinase Inhibitor Y- ...
Calmodulin-dependent kinase II and Rho-kinase are also found to phosphorylate calponin at Ser175 and Thr184 in vitro. Of these ... the main site of regulatory phosphorylation by calmodulin-dependent kinase II and Rho-kinase is Ser175. Dephosphorylation of ... "Identification of calponin as a novel substrate of Rho-kinase". Biochemical and Biophysical Research Communications. 273 (1): ... Nonetheless, CH domain in calponin was found to bind to extra-cellular regulated kinase (ERK) for calponin to play a possible ...
"Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase". Science. 285 (5429): 895-8. doi: ... "Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase". Science. 285 (5429): 895-8. doi: ... "Activation of LIM kinases by myotonic dystrophy kinase-related Cdc42-binding kinase alpha". J. Biol. Chem. 276 (25): 23092-6. ... "Cofilin Phosphorylation by Protein Kinase Testicular Protein Kinase 1 and Its Role in Integrin-mediated Actin Reorganization ...
Rho kinase inhibitor Williams RD, Novack GD, van Haarlem T, Kopczynski C (November 2011). "Ocular hypotensive effect of the Rho ... Verosudil (AR-12286) is a drug which acts as a potent and selective inhibitor of the enzyme Rho kinase, and has been ... Skaat A, Jasien JV, Ritch R (September 2016). "Efficacy of Topically Administered Rho-Kinase Inhibitor AR-12286 in Patients ... kinase inhibitor AR-12286 in patients with glaucoma and ocular hypertension". American Journal of Ophthalmology. 152 (5): 834- ...
Ohashi K, Nagata K, Maekawa M, Ishizaki T, Narumiya S, Mizuno K (2000). "Rho-associated kinase ROCK activates LIM-kinase 1 by ... "Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase". Science. 285 (5429): 895-8. doi: ... "Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase". Science. 285 (5429): 895-8. doi: ... "Activation of LIM kinases by myotonic dystrophy kinase-related Cdc42-binding kinase alpha". J. Biol. Chem. 276 (25): 23092-6. ...
Nerve conduction velocity
Studies have shown that the Rho/Rho-kinase signaling pathway is more active in individuals with diabetes and that this ... Therefore, over-activity of the Rho/Rho-kinase signaling pathway may inhibit nerve conduction. Motor nerve conduction velocity ... "The Rho-kinase inhibitor fasudil restores normal motor nerve conduction velocity in diabetic rats by assuring the proper ...
Mir-10 microRNA precursor family
This results in upregulation of RhoA/RhoC, Rho kinase activation and tumour cell invasion. MicroRNA Gene expression Hox genes ... leading to Rho-kinase-associated cytoskeleton activation and breast tumor cell invasion". The Journal of Biological Chemistry. ... "Targeting of syndecan-1 by microRNA miR-10b promotes breast cancer cell motility and invasiveness via a Rho-GTPase- and E- ...
"Citron rho-interacting kinase, a novel tissue-specific ser/thr kinase encompassing the Rho-Rac-binding protein Citron". The ... kinase activity. • protein serine/threonine kinase activity. • GO:0001948 protein binding. • ATP binding. • Rho GTPase binding ... Dephospho-(reductase kinase) kinase (EC 22.214.171.124). *AMP-activated protein kinase α *PRKAA1 ... Myosin-heavy-chain kinase (EC 126.96.36.199). *Aurora kinase *Aurora A kinase ...
Borikova, A. L.; Dibble, C. F.; Sciaky, N.; Welch, C. M.; Abell, A. N.; Bencharit, S.; Johnson, G. L. (2010). "Rho Kinase ... This protein is also involved in regulating the cellular localization of the KRIT1 protein and acts with the Rho Kinase ... The normal function of malcavernin is to act as a scaffold for a variety of signaling complexes including p38 MAP Kinase. ... "The Cerebral Cavernous Malformation signaling pathway promotes vascular integrity via Rho GTPases". Nature Medicine. 15 (2): ...
"Nm23-H1 metastasis suppressor phosphorylation of kinase suppressor of Ras via a histidine protein kinase pathway". J. Biol. ... "Association of CNK1 with Rho guanine nucleotide exchange factors controls signaling specificity downstream of Rho". Curr. Biol ... Connector enhancer of kinase suppressor of ras 1 is an enzyme that in humans is encoded by the CNKSR1 gene. This gene is a ... "Entrez Gene: CNKSR1 connector enhancer of kinase suppressor of Ras 1". Jaffe AB, Aspenström P, Hall A (Feb 2004). "Human CNK1 ...
Borikova AL, Dibble CF, Sciaky N, Welch CM, Abell AN, Bencharit S, Johnson GL (Apr 2010). "Rho kinase inhibition rescues the ... "The prooncoprotein EWS binds calmodulin and is phosphorylated by protein kinase C through an IQ domain". The Journal of ...
p21-activated kinases (PAKs) 1, 2 and 3 via SH3 domain. c-Cbl via SH3 domain. Rho family GTP-binding protein family members ... Manser E, Loo TH, Koh CG, Zhao ZS, Chen XQ, Tan L, Tan I, Leung T, Lim L (Jul 1998). "PAK kinases are directly coupled to the ... Rho guanine nucleotide exchange factor 6 is a protein that, in humans, is encoded by the ARHGEF6 gene. ARHGEF6 is commonly ... Rho family of GTPases Scaffold protein Guanine nucleotide exchange factor X-linked intellectual disability GRCh38: Ensembl ...
RSK2 is normally activated by the ERK MAP kinase. Mutated RSK2 may be deficient for activation by ERK, or its kinase activity ... Mutations in the RPS6KA3 gene can result in expression of an RSK2 protein (ribosomal S6 kinase 2) with reduced or absent kinase ... RSK2 is a downstream component of the MAPK (mitogen-activated protein kinase) cascade that is itself a kinase. RSK2 ... Decreased ribosomal S6 kinase activity in cultured fibroblast or transformed lymphoblast cells from a male indicates Coffin- ...
1999). "Phosphorylation of adducin by Rho-kinase plays a crucial role in cell motility". J. Cell Biol. 145 (2): 347-61. doi: ... Adducin binds with high affinity to Ca(2+)/calmodulin and is a substrate for protein kinases A and C. Alternative splicing ... Matsuoka Y, Li X, Bennett V (1998). "Adducin is an in vivo substrate for protein kinase C: phosphorylation in the MARCKS- ... Definition of the calmodulin-binding domain and sites of phosphorylation by protein kinases A and C". J. Biol. Chem. 271 (41): ...
... interacts with two Rho-specific GEFs (Net1 and p115RhoGEF) and two kinases of the JNK MAP kinase pathway (MLK2 and MKK7). He ... Ga13 activates p115 Rho GEF, which in turn activates Rho), but it was also known that Gaq does not activate p115 Rho GEF, and ... This led to the conclusion that CNK1 couples specific Rho exchange factors to the JNK MAP kinase pathway, providing specificity ... Hall concluded that Rac and Rho are complementary for polymerised actin organisation. Indeed, Rho-dependent response is ...
Brain-derived neurotrophic factor
Tropomyosin receptor kinase B § Agonists. References. *^ a b c GRCh38: Ensembl release 89: ENSG00000176697 - Ensembl, May ... Penzes P, Johnson RC, Sattler R, Zhang X, Huganir RL, Kambampati V, Mains RE, Eipper BA (January 2001). "The neuronal Rho-GEF ... positive regulation of non-membrane spanning protein tyrosine kinase activity. • transmembrane receptor protein tyrosine kinase ... The TrkB receptor is encoded by the NTRK2 gene and is member of a receptor family of tyrosine kinases that includes TrkA and ...
Tumor necrosis factor alpha
"TNF-stimulated MAP kinase activation mediated by a Rho family GTPase signaling pathway". Genes Dev. 25 (19): 2069-78. doi: ... TRAF2 in turn recruits the multicomponent protein kinase IKK, enabling the serine-threonine kinase RIP to activate it. An ... TRAF2/Rac activates the JNK-inducing upstream kinases of MLK2/MLK3, TAK1, MEKK1 and ASK1 (either directly or through GCKs ... I-kappaB kinase/NF-kappaB signaling. • activation of MAPKKK activity. • positive regulation of translational initiation by iron ...
Wiskott-Aldrich syndrome protein
protein kinase binding. • small GTPase binding. • Rac GTPase binding. Cellular component. • cytoplasm. • cell-cell junction. • ... Rho protein signal transduction. • regulation of actin polymerization or depolymerization. • regulation of lamellipodium ... and the Fyn protein-tyrosine kinase". Molecular Biology Reports. 26 (3): 173-7. doi:10.1023/A:1006954206151. PMID 10532312.. ... is a binding partner for c-Src family protein-tyrosine kinases". Current Biology. 6 (8): 981-8. doi:10.1016/s0960-9822(02)00642 ...
Proteiinkinaasid - Vikipeedia
"Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification". FASEB J ... Rho-sõltuv proteiinkinaas. *Tsükliinisõltuvad kinaasid. Viited[muuda , muuda lähteteksti]. *↑ "Meditsiinisõnastik", tõlkijad ... Dan R Robinson, Yi-Mi Wu ja Su-Fang Lin, The protein tyrosine kinase family of the human genome, 20 November 2000, Volume 19, ... Steven K Hanks, Genomic analysis of the eukaryotic protein kinase superfamily: a perspective, Genome Biol. 2003; 4(5): 111, ...
From left to right are: immunoglobulin G (IgG, an antibody), hemoglobin, insulin (a hormone), adenylate kinase (an enzyme), and ... Samarin S, Nusrat A (January 2009). "Regulation of epithelial apical junctional complex by Rho family GTPases". Frontiers in ... Domains usually also have specific functions, such as enzymatic activities (e.g. kinase) or they serve as binding modules (e.g ...
GTP-binding protein regulators
... bind to the GDP-bound form of Rho and Rab small GTPases and not only prevent exchange (maintaining the small GTPase in an off- ... Other protein kinase. Serine/threonine:. *Casein kinase *1. *2. *eIF-2 kinase *EIF2AK3 ...
Generation of pressure is dependent on formin-mediated F-actin nucleation and Rho kinase (ROCK)-mediated myosin II ... cyclin-dependent kinases, and other cell cycle proteins. The phases follow one another in strict order and there are " ...
Serine/threonine kinase. *RPS6KA3 *Coffin-Lowry syndrome. *CHEK2 *Li-Fraumeni syndrome 2 ... RHO: RAC2 *Neutrophil immunodeficiency syndrome. *ARF: SAR1B *Chylomicron retention disease. *ARL13B *Joubert syndrome 8 ...
Kim JM, Sohn HY, Yoon SY, Oh JH, Yang JO, Kim JH, Song KS, Rho SM, Yoo HS, Yoo HS, Kim YS, Kim JG, Kim NS (2005). " ... PARP1 is over-expressed in tyrosine kinase-activated leukemias, in neuroblastoma, in testicular and other germ cell ... "c-MYC Generates Repair Errors via Increased Transcription of Alternative-NHEJ Factors, LIG3 and PARP1, in Tyrosine Kinase- ...
Factor de necrose tumoral alfa, a enciclopedia libre
"TNF-stimulated MAP kinase activation mediated by a Rho family GTPase signaling pathway". Genes Dev 25 (19): 2069-78. PMC ...
Yersinia pseudotuberculosis, a enciclopedia libre
Galyov EE, Håkansson S, Forsberg A, Wolf-Watz H (1993). "A secreted protein kinase of Yersinia pseudotuberculosis is an ... YopT únese á Rho GTPase, normalmente chamada "RhoA", e desacóplaa da membrana, deixándoa nun estado inactivo como RhoA-GDI ( ... enterocolitica promotes deactivation of macrophage mitogen-activated protein kinases extracellular signal-regulated kinase-1/2 ... undida ao inhibidor da disociación do nucleótido guanina), mentres que YopE e YpkA converten as proteínas Rho ao seu estado ...
Napetostni kalcijev kanalček - Wikipedija, prosta enciklopedija
Rho-associated kinase-mediated phosphorylation of MYPT1 at Thr-855 but not Thr-697" (PDF).. ...
Rho-associated kinase-mediated phosphorylation of MYPT1 at Thr-855 but not Thr-697" (PDF). Biochem. J. 389 (Pt 3): 763-74. doi: ... The rise in intracellular calcium complexes with calmodulin, which in turn activates myosin light-chain kinase. This enzyme is ...
"An SH3 domain-containing GTPase-activating protein for Rho and Cdc42 associates with focal adhesion kinase". Molecular and ... protein kinase activity. • JUN kinase binding. • non-membrane spanning protein tyrosine kinase activity. • transferase activity ... FAK（focal adhesion kinase、フォーカルアドヒージョンキナーゼ、焦点接着キナーゼ、接着斑キナーゼ）またはPTK2（protein tyrosine kinase 2）は、ヒトではPTK2遺伝子にコードされるタンパク質である。 ... "Janus kinases and focal adhesion kinases play in the 4.1
Protein kinase C activation. PIP2 cleavage to IP3 and DAG initiates intracellular calcium release and PKC activation. ... Diacylglycerol can be phosphorylated to phosphatidic acid by diacylglycerol kinase. Insulin resistance. Activation of PKC ... whereas DAG is a physiological activator of protein kinase C (PKC). The production of DAG in the membrane facilitates ... "Protein Kinase C as the Receptor for the Phorbol Ester Tumor Promoters: Sixth Rhoads Memorial Award Lecture". Cancer Research ...
... which activates downstream effectors like Rho GTPase and Rho-associated kinase (ROCK), which activates actin and cytoskeleton ... leading to the activation of small GTPases Rho and Rac. For the Rho branch, Wnt signals induce DVL to form a complex with ... Activating the Rac GTPase stimulates the downstream effector c-Jun N-terminal kinase (JNK), which controls rearrangements in ... Daam1 (Dishevelled associated activator of morphogenesis 1). This complex then interacts with Rho guanine nucleotide ...
"Histone acetyltransferases: Rising ancient counterparts to protein kinases". Biopolymers. 99 (2): 98-111. doi:10.1002/bip. ... inquiry regarding the role of acetyltransferases in signal transduction pathways and whether an appropriate analogy to kinases ...
"Intracellular substrates of brain-enriched receptor protein tyrosine phosphatase rho (RPTPrho/PTPRT)". Brain Research. 1116 (1 ... "Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complexes". The Journal of Cell Biology. 128 (5): ... "The tyrosine kinase substrate p120cas binds directly to E-cadherin but not to the adenomatous polyposis coli protein or alpha- ... "Interaction of glycogen synthase kinase 3beta with the DF3/MUC1 carcinoma-associated antigen and beta-catenin". Molecular and ...
PARD6A - ويكيبيديا
Rho GTPase binding. • protein kinase C binding. المكونات الخلوية. • عصارة خلوية. • إسقاط خلية. • غشاء. • bicellular tight ... Joberty G، Petersen C، Gao L، Macara IG (2000). "The cell-polarity protein Par6 links Par3 and atypical protein kinase C to ... "The mammalian homologue of the Caenorhabditis elegans polarity protein PAR-6 is a binding partner for the Rho GTPases Cdc42 and ... "Partitioning-defective protein 6 regulates insulin-dependent glycogen synthesis via atypical protein kinase C.". Mol. ...
1omw: Crystal Structure of the complex between G Protein-Coupled Receptor Kinase 2 and Heterotrimeric G Protein beta 1 and ... Buhl AM, Osawa S, Johnson GL (1995). "Mitogen-activated protein kinase activation requires two signal inputs from the human ... 2bcj: Crystal Structure of G Protein-Coupled Receptor Kinase 2 in Complex with Galpha-q and Gbetagamma Subunits ... "Mutational analysis of Gbetagamma and phospholipid interaction with G protein-coupled receptor kinase 2". J. Biol. Chem. 275 ( ...
MAP kinase (MAPK), pp60(c-src), and the downstream targets of Rho kinase (ROK). RHAMM can also cooperate with CD44 to ... In terms of mechanics, RHAMM promotes cancer cell motility through a number of pathways including focal adhesion kinase (FAK), ... It forms links with several protein kinases associated with cell locomotion, for example, extracellular signal-regulated ... the activation of Rho GTPases can promote epithelial-mesenchymal transition (EMT) of the cancer cells. During the processes of ...
... rho associated coiled-coil-containing protein kinase 1).. *Formation of membrane protrusions: Some cell types, under ... Finally, the Akt protein kinase promotes cell survival through two pathways. Akt phosphorylates and inhibits Bad (a Bcl-2 ...
Farnesoid X receptor
negative regulation of I-kappaB kinase/NF-kappaB signaling. • negative regulation of tumor necrosis factor-mediated signaling ...
鈉鉀泵 - 维基百科，自由的百科全书
Regulation of Na+-K+-ATPase by cAMP-dependent protein kinase anchored on membrane via its anchoring protein Kinji Kurihara, ... mitogen-activated protein kinase, MAPK)訊息的梯瀑效應(cascade)的活化、粒線體活性氧（reactive oxygen species, ROS）的產生、C型磷脂酶（phospholipase C
mitogen-activated protein kinase kinase kinase binding. • protein binding. • thioesterase binding. • protein kinase binding. • ... Rho GDP-dissociation inhibitor binding. • ubiquitin protein ligase activity. • apolipoprotein A-I receptor binding. • GTP- ... "The MAP kinase kinase kinase MLK2 co-localizes with activated JNK along microtubules and associates with kinesin superfamily ... regulation of protein kinase activity. • regulation of attachment of spindle microtubules to kinetochore. • regulation of small ...
Protein arginine methyltransferase 5
Rho J, Choi S, Seong YR, Cho WK, Kim SH, Im DS (2001). "Prmt5, which forms distinct homo-oligomers, is a member of the protein- ... "Interaction of the somatostatin receptor subtype 1 with the human homolog of the Shk1 kinase-binding protein from yeast". J. ... "The human homologue of the yeast proteins Skb1 and Hsl7p interacts with Jak kinases and contains protein methyltransferase ... "The human homologue of the yeast proteins Skb1 and Hsl7p interacts with Jak kinases and contains protein methyltransferase ...
Rho kinase inhibitor - Wikipedia
Rho-kinase inhibitors (rho-associated protein kinase inhibitor or ROCK inhibitor) are a series of compounds that target rho ... Rho kinase inhibitor also functions by blocking rho-mediated dephosphorylation of MLC20. A number of Rho kinase inhibitors are ... Molecular Mechanism: Rho kinase inhibitors act on Rho kinase by altering the conformation of the protein, disrupting ... "Rho kinase inhibitor HA-1077 prevents Rho-mediated myosin phosphatase inhibition in smooth muscle cells". American Journal of ...
Rho-associated protein kinase - Wikipedia
Rho-associated protein kinase (ROCK) is a kinase belonging to the AGC (PKA/ PKG/PKC) family of serine-threonine kinases. It is ... binding kinases (MRCK) and citron kinase. All of these kinases are composed of a N-terminal kinase domain, a coiled-coil ... "Roles of Rho-associated kinase in cytokinesis; mutations in Rho-associated kinase phosphorylation sites impair cytokinetic ... Thus, the kinase activity is off when ROCK is intramolecularly folded. The kinase activity is switched on when Rho-GTP binds to ...
Rho-associated protein kinase 2 (IPR029878) | InterPro | EMBL-EBI
Rho-associated protein kinase 2 (IPR029878). Short name: ROCK2 Family relationships *Rho-associated protein kinase 1/2 ( ... Rho-associated protein kinases (ROCKs) were originally identified as small GTPase Rho effectors. Later, ROCKs were found ... Rho-kinase inhibitors as therapeutics: from pan inhibition to isoform selectivity.. Cell. Mol. Life Sci. 67 171-7 2010 ... Rho-associated coiled-coil kinase (ROCK) signaling and disease.. Crit. Rev. Biochem. Mol. Biol. 48 301-16 2013 ...
JCI - Rho-kinase/AMPK axis regulates hepatic lipogenesis during overnutrition
FERONIA receptor-like kinase regulates RHO GTPase signaling of root hair development | PNAS
FERONIA receptor-like kinase regulates RHO GTPase signaling of root hair development. Qiaohong Duan, Daniel Kita, Chao Li, ... FERONIA receptor-like kinase regulates RHO GTPase signaling of root hair development ... 2005) Kinase partner protein interacts with the LePRK1 and LePRK2 receptor kinases and plays a role in polarized pollen tube ... FERONIA receptor-like kinase regulates RHO GTPase signaling of root hair development ...
Rho kinase is required for CCR7-m... preview & related info | Mendeley
We studied the role of Rho kinase and extracellular signal-regulated kinase (ERK)-2 in the polarization and migration of T ... Both Rho kinase protein isoforms are expressed in T lymphocytes. Inhibition of the Rho kinases with Y-27632 strongly inhibited ... We studied the role of Rho kinase and extracellular signal-regulated kinase (ERK)-2 in the polarization and migration of T ... Rho kinase is required for CCR7-mediated polarization and chemotaxis of T lymphocytes. *Bardi G ...
Rho Kinase in Patients With Atherosclerosis - Full Text View - ClinicalTrials.gov
Rho Kinase (ROCK) Inhibition in Carotid Atherosclerosis - Tabular View - ClinicalTrials.gov
Rho Kinase (ROCK) Inhibition in Carotid Atherosclerosis Official Title ICMJE The Effect of Fasudil on Rho Kinase Activity in ... To evaluate the causal relationship between Rho/Rho kinase overactivity and mechanisms of vascular dysfunction in patients with ... Rho Kinase (ROCK) Inhibition in Carotid Atherosclerosis. The safety and scientific validity of this study is the responsibility ... We anticipated that Rho/ROCK expression and activity would be decreased in spcimens obtained from fasudil treated patients ...
The Prognostic Values of Leukocyte Rho Kinase Activity in Acute Ischemic Stroke
H. Kajimoto, K. Hashimoto, S. N. Bonnet et al., "Oxygen activates the rho/rho-kinase pathway and induces RhoB and ROCK-1 ... T. Nakakuki, M. Ito, H. Iwasaki et al., "Rho/Rho-kinase pathway contributes to C-reactive protein-induced plasminogen activator ... "Dependence of proliferating dedifferentiated vascular smooth muscle contraction on Rho-Rho kinase system," Trends in ... The Prognostic Values of Leukocyte Rho Kinase Activity in Acute Ischemic Stroke. Cheng-I. Cheng,1,2 Yu-Chun Lin,1,2 Tzu-Hsien ...
Rho-kinase activation is involved in hypoxia-induced pulmonary vasoconstriction. - PubMed - NCBI
In summary, the data show that Rho-kinase is activated by hypoxia in PASMCs, and Rho/Rho-kinase is functionally linked to ... Rho-associated serine/threonine kinase (Rho-kinase) is a downstream effector of small GTPase RhoA that has recently been shown ... a Rho-kinase inhibitor), exoenzyme C3 (a specific Rho inhibitor), or toxin B (an inhibitor for Rho proteins). In addition, ... The present study investigated the role of Rho/ Rho-kinase in hypoxia-induced pulmonary vasoconstriction (HPV). Small pulmonary ...
hCLOCK Causes Rho-Kinase-Mediated Endothelial Dysfunction and NF-κB-Mediated Inflammatory Responses
... Xiao Tang,1 Daqiao Guo,1 ... A Rho inhibitor allows specific study of this Rho pathway and uncovers alternate pathways of ROS production. A ROS scavenger ... ROCK1 is a major downstream effector of the Rho GTPases, in particular RhoA. These Rho GTPases are regulated by GTPase- ... Additionally, the Rho GTPases and the NF-κB pathway had both been implicated in the inflammatory response. We sought to find ...
RCSB PDB - Gene View - ROCK2 - Rho associated coiled-coil containing protein kinase 2
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Study identifies optimal dose of promising Rho kinase inhibitor - American Academy of Ophthalmology
... a rho kinase inhibitor, is the most optimal for controlling IOP over ... Rho kinase inhibitors have been shown to reduce IOP in rabbits and monkeys by increasing aqueous humor drainage through the ... This prospective, randomized, multi-center phase 2 study found that the 0.4% dose of K-115, a rho kinase inhibitor, is the most ... and clinical studies in which similar conjunctival hyperemia was identified after instillation of higher doses of Rho kinase ...
RCSB PDB - Protein Feature View - Rho-associated protein kinase 1 - Q13464 (ROCK1 HUMAN)
Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle ... RHOA binding leads to a conformation change and activation of the kinase. Truncated ROCK1 is constitutively activated. UniProt ... The C-terminal auto-inhibitory domain interferes with kinase activity. ...
Rho Kinase Inhibition: A New Approach for Treating Diabetic Nephropathy? | Diabetes
ROCK, Rho kinase. Rho family GTPases have received increasing attention as critical regulators of cell function (1). Initially ... RhoA is one of the most widely studied of the 22 mammalian members of the family, and the serine-threonine kinase Rho kinase ( ... Budzyn K, Marley PD, Sobey CG: Targeting Rho and Rho-kinase in the treatment of cardiovascular disease. Trends Pharmacol Sci27 ... Rho Kinase Inhibition: A New Approach for Treating Diabetic Nephropathy? Message Subject (Your Name) has forwarded a page to ...
CIT - Citron Rho-interacting kinase - Homo sapiens (Human) - CIT gene & protein
IPR000961. AGC-kinase_C. IPR017405. Citron_Rho-interacting_kinase. IPR001180. CNH_dom. IPR002219. PE/DAG-bd. IPR011993. PH-like ... IPR000961. AGC-kinase_C. IPR017405. Citron_Rho-interacting_kinase. IPR001180. CNH_dom. IPR002219. PE/DAG-bd. IPR011993. PH-like ... Citron Rho-interacting kinaseImported. ,p>Information which has been imported from another database using automatic procedures ... tr,H7BYJ3,H7BYJ3_HUMAN Citron Rho-interacting kinase (Fragment) OS=Homo sapiens GN=CIT PE=1 SV=1 ...
Drk-mediated signaling to Rho kinase is required for anesthesia-resistant memory in Drosophila. - PubMed - NCBI
Drk-mediated signaling to Rho kinase is required for anesthesia-resistant memory in Drosophila.. Kotoula V1, Moressis A1, ... Significantly, Drk signals engage the Rho kinase Drok, implicating dynamic cytoskeletal changes in ARM, and this is supported ... Drk-mediated signaling to Rho kinase is required for anesthesia-resistant memory in Drosophila ... Drk-mediated signaling to Rho kinase is required for anesthesia-resistant memory in Drosophila ...
Rho kinase inhibitors block melanoma cell migration and inhibit metastasis. | Sigma-Aldrich
Rho kinase inhibitors block melanoma cell migration and inhibit metastasis.. [Amine Sadok, Afshan McCarthy, John Caldwell, Ian ... These compounds also inhibit the Rho-kinases ROCK 1 and ROCK 2 and we show they potently inhibit ROCK activity in melanoma ... Fragment-based screening has led to the discovery of orally available, ATP-competitive AKT kinase inhibitors, AT13148 and ...
ROCK2 - Rho-associated protein kinase 2 - Bos taurus (Bovine) - ROCK2 gene & protein
Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle ... "Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho.". Matsui T., ... "Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho.". Matsui T., ... "Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho.". Matsui T., ...
Bioaxone Biosciences receives Fast-Track SBIR grant to assess potential of Rho Kinase 2 inhibitor
Rho Kinase Regulates Schwann Cell Myelination and Formation of Associated Axonal Domains | Journal of Neuroscience
Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase). Science 273: 245-248. ... Both drugs have an affinity for Rho kinases that is at least 20-30 times higher than those for other Rho effector kinases, ... Oshiro N, Fukata Y, Kaibuchi K (1998) Phosphorylation of moesin by Rho-associated kinase (Rho-kinase) plays a crucial role in ... A key effector of Rho is Rho kinase (ROCK), a serinethreonine kinase that regulates actin polymerization and myosin activity ( ...
Formation of Actin Stress Fibers and Focal Adhesions Enhanced by Rho-Kinase | Science
Binding of Rho to Rho-kinase was determined by overlay assay as described (10). Purified Rho-kinase (0.25 μg) or GST-RB (2.5 μg ... include protein kinase N (PKN) (9), Rho-kinase (10) [also called Rho-binding kinase (11)], and the myosin-binding subunit (MBS ... Rho-kinase is activated by Rho and may mediate some biological effects of Rho. Microinjection of the catalytic domain of Rho- ... 1C). The kinase activity of Rho-kinase was not affected by GST-CAT-KD, GST-COIL, or GST-PH (20). The kinase activity of PKN and ...
Screening for cell migration inhibitors via automated microscopy reveals a Rho-kinase inhibitor
We have discovered an inhibitor of Rho-kinase (ROCK) through an image-based, high-throughput screen of cell monolayer wound ... Small-molecule kinase inhibitors are predominantly discovered in pure protein assays. ... Rockout inhibits blebbing and causes dissolution of actin stress fibers, phenocopying Rho-kinase inhibitors. Testing Rho-kinase ... Screening for cell migration inhibitors via automated microscopy reveals a Rho-kinase inhibitor Chem Biol. 2005 Mar;12(3):385- ...
Rho kinase 2 | definition of Rho kinase 2 by Medical dictionary
Rho kinase 2 explanation free. What is Rho kinase 2? Meaning of Rho kinase 2 medical term. What does Rho kinase 2 mean? ... Looking for online definition of Rho kinase 2 in the Medical Dictionary? ... Rho kinase 2 , definition of Rho kinase 2 by Medical dictionary https://medical-dictionary.thefreedictionary.com/Rho+kinase+2 ... redirected from Rho kinase 2) ROCK2. A gene on chromosome 2p24 that encodes a protein kinase which is a key regulator of actin ...
IJMS | Free Full-Text | Fasudil, a Rho-Kinase Inhibitor, Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice
The small GTPase, RhoA, and its target protein, Rho-kinase (ROCK), may interact with other signaling pathways known to ... "Fasudil, a Rho-Kinase Inhibitor, Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice." Int. J. Mol. Sci. 13, no. 7: 8293- ... Fasudil, a Rho-Kinase Inhibitor, Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice. Chunguo Jiang 1. ... Jiang C, Huang H, Liu J, Wang Y, Lu Z, Xu Z. Fasudil, a Rho-Kinase Inhibitor, Attenuates Bleomycin-Induced Pulmonary Fibrosis ...
Rho Kinase Inhibition as a Therapeutic for Progressive Supranuclear Palsy and Corticobasal Degeneration | Journal of...
Rho-associated coiled-coil containing protein kinases 1 (ROCK1) and ROCK2 are ubiquitous serine/threonine kinases that share 65 ... Here, we report that protein levels of the Rho-associated protein kinases (ROCK1 and ROCK2), p70 S6 kinase (S6K), and mammalian ... 2011) Rho kinase II phosphorylation of the lipoprotein receptor LR11/SORLA alters amyloid-beta production. J Biol Chem 286:6117 ... 1997) Formation of actin stress fibers and focal adhesions enhanced by Rho-kinase. Science 275:1308-1311, doi:10.1126/science. ...
Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase)
The small guanosine triphosphatase Rho is implicated in myosin light chain (MLC) phosphorylation, which results in contraction ... Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase) Science. 1996 Jul 12;273(5272):245-8. doi: ... Rho-associated kinase (Rho-kinase), which is activated by GTP.RhoA, phosphorylated MBS and consequently inactivated myosin ... Thus, Rho appears to inhibit myosin phosphatase through the action of Rho-kinase. ...
Molecules | Free Full-Text | The Vasorelaxant Mechanisms of a Rho Kinase Inhibitor DL0805 in Rat Thoracic Aorta
The Rho-kinase signaling pathway is substantially involved in vascular contraction. The aim of the present study was to ... evaluate the vasorelaxant effects of Rho kinase inhibitor DL0805 in isolated rat aortic rings and to investigate its possible ... These findings suggested that DL0805 is a novel vasorelaxant compound associated with inhibition of Rho/ROCK signaling pathway ... Rho-kinase has been suggested as a potential therapeutic target in the treatment of cardiovascular diseases. ...
Frontiers | ROCKing Regeneration: Rho Kinase Inhibition as Molecular Target for Neurorestoration | Frontiers in Molecular...
One key mediator of growth inhibitory signaling is Rho-associated kinase (ROCK), which has been shown to modulate growth cone ... One key mediator of growth inhibitory signaling is Rho-associated kinase (ROCK), which has been shown to modulate growth cone ... Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase). Science 273, 245-248. ... Rho Kinase (ROCK). The ROCK proteins are serine/threonine kinases with a large homology to other AGC kinases, such as myotonic ...
Regulation of JNK kinase signaling modules by Rho activated kinase, ROCK1 | Cancer Research
Regulation of JNK kinase signaling modules by Rho activated kinase, ROCK1. Pat P. Ongusaha, Young-Bum Kim, Hank H. Qi, Roger ... Regulation of JNK kinase signaling modules by Rho activated kinase, ROCK1. Pat P. Ongusaha, Young-Bum Kim, Hank H. Qi, Roger ... Regulation of JNK kinase signaling modules by Rho activated kinase, ROCK1. Pat P. Ongusaha, Young-Bum Kim, Hank H. Qi, Roger ... Regulation of JNK kinase signaling modules by Rho activated kinase, ROCK1 Message Subject (Your Name) has forwarded a page to ...
RhoAPathwayInhibitorsGTPaseGTPasesROCK2Role of Rho kinaseEffectorsPhosphorylationProteinsFasudilRegulatesInhibitPhosphorylatesMitogen-activaCytoskeletonContractionPhosphatidylinositol 3 kinaROCKSubstratesEffector Rho kinaseInhibitor Y-27632ActivatesAtherosclerosisVascularSignal transductionStress fibersRegulationPathwaysMembers of the Rho familyEndothelialSpecific Rho-kinase inhibitorSerine-threoniForms of Rho-kinaseSelectiveRolesIsoform of Rho-kinaseShown that Rho-kinaseActivation of Rho-kinaseInvolvement of Rho-kinaseInhibition of Rho kinasesMediatesTyrosine kinaseY27632MolecularCardiovascular diseasesInhibitsMiceFunctionallyMammalianExtracellular
- Molecular Mechanism: Rho kinase inhibitors act on Rho kinase by altering the conformation of the protein, disrupting translocation to the plasma membrane, preventing ATP-dependent phosphorylation, and blocking RhoA binding to ROCK. (wikipedia.org)
- Rho-associated serine/threonine kinase (Rho-kinase) is a downstream effector of small GTPase RhoA that has recently been shown to play an important role in regulating smooth muscle contraction. (nih.gov)
- Mammalian ROCK consists of a kinase domain, a coiled-coil region and a Pleckstrin homology (PH) domain, which reduces the kinase activity of ROCKs by an autoinhibitory intramolecular fold if RhoA-GTP is not present. (wikipedia.org)
- RHOA binding leads to a conformation change and activation of the kinase. (rcsb.org)
- RhoA is one of the most widely studied of the 22 mammalian members of the family, and the serine-threonine kinase Rho kinase (ROCK) is a major RhoA effector. (diabetesjournals.org)
- Although GST-RB inhibited Rho-kinase activity stimulated by GTP-γ-S·GST-RhoA in a dose-dependent manner, it did not affect the kinase activity of GST-CAT (Fig. 1 C). The kinase activity of Rho-kinase was not affected by GST-CAT-KD, GST-COIL, or GST-PH ( 20 ). (sciencemag.org)
- The small GTPase, RhoA, and its target protein, Rho-kinase (ROCK), may interact with other signaling pathways known to contribute to pulmonary ﬁbrosis. (mdpi.com)
- Rho-associated kinase (Rho-kinase), which is activated by GTP.RhoA, phosphorylated MBS and consequently inactivated myosin phosphatase. (nih.gov)
- Rho-associated kinases (Rho kinases), which are downstream effectors of RhoA GTPase, regulate diverse cellular functions including actin cytoskeletal organization. (biologists.org)
- Although there is considerable evidence that Rho kinases mediate many in vivo functions of RhoA, their roles in regulating embryonic morphogenesis remain unknown. (biologists.org)
- RhoA-GTP binds to the RBD domain of ROCK and releases the kinase domain of ROCK leading to the activation of ROCK (Leung et al. (atlasgeneticsoncology.org)
- A secondary pathway for vascular smooth muscle contraction that is not directly dependent on Ca(2+) concentration, but rather mediating Ca(2+) sensitization, is the RhoA/Rho kinase pathway. (medworm.com)
- In response to contractile stimuli, the small GTPase RhoA activates its downstream effector Rho kinase which, in turn, promotes contraction via myosin light chain phosphatase (MLCP) inhibition. (medworm.com)
- RhoA/Rho kinase-mediated MLCP inhibition occurs mainly by phosphorylation and inhibition of MYPT1, the regulatory subunit of MLCP, or by CPI-17-mediated inhibition of the catalytic subunit of MLCP. (medworm.com)
- 1,2 The effector domains of RhoA, RhoB, and RhoC (collectively referred to here as Rho) have the same amino acid sequence, and these G proteins appear to have similar intracellular targets. (ahajournals.org)
- Because dys-regulation of RhoA/Rho kinase pathway is implicated in increased vascular contractility, we examined whether TCTP induces alterations in RhoA pathway in vascular smooth muscle cells (VSMCs). (mdpi.com)
- Conversely, lentiviral silencing of TCTP reduced the RhoA expression and Rho kinase signalings. (mdpi.com)
- Maeng J, Sheverdin V, Shin H, Ha I, Bae SS, Yang-Yen H-F, Lee K. Up-Regulation of Rhoa/Rho Kinase Pathway by Translationally Controlled Tumor Protein in Vascular Smooth Muscle Cells. (mdpi.com)
- The RHO-family proteins RAC1, CDC42, and RHOA are small GTP-binding proteins that act as molecular switches, shifting between an inactive, GDP-bound form and an active, GTP-bound form that define functions of RHO GTPases. (aacrjournals.org)
- The three best studied members of the RHO family, RAC1, CDC42, and RHOA, are essential for transformation by activated RAS ( 3, 4 ), and, in the case of RAC1 and RAC2, themselves can be oncogenic drivers in human malignancies ( 5, 6 ). (aacrjournals.org)
- RHOA has a distinct set of effector kinases, including the ROCK, CITRON, and PRK1, all of which regulate cellular processes that contribute to tumorigenesis, invasion, and metastasis ( 12 ). (aacrjournals.org)
- 2017. "Ceramide activation of RhoA/Rho kinase impairs actin polymerization during aggregated LDL catabolism[S]." Journal of Lipid Research 58 (10): 1977-1987. (harvard.edu)
- We demonstrate that knockdown of RhoA or inhibition of Rho kinase restores agLDL-induced actin polymerization in SK2KO macrophages. (harvard.edu)
- These findings highlight a critical regulatory pathway by which ceramide impairs actin polymerization through increased RhoA/Rho kinase signaling and regulates foam cell formation. (harvard.edu)
- Such disease states are often associated with increased vascular RhoA/Rho-kinase activity and decreased activity of nitric oxide (NO). This study tested whether female gender is associated with lower Rho-kinase activity or higher NO activity in cerebral arteries in vivo and whether estrogen contributes to any such gender differences. (ahajournals.org)
- Vascular expression of RhoA or Rho-kinase was assessed by Western blotting. (ahajournals.org)
- Expression of total RhoA or Rho-kinase did not differ between males and females. (ahajournals.org)
- Activation of the G protein RhoA and its downstream effector, Rho-kinase, results in decreased myosin light chain phosphatase activity. (ahajournals.org)
- There is increasing functional evidence that vascular NO signaling may interact with and inhibit activity of the RhoA/Rho-kinase pathway. (ahajournals.org)
- For example, one of the mechanisms of NO-induced aortic relaxation appears to be via inhibition of RhoA/Rho-kinase-mediated contraction. (ahajournals.org)
- Transgenic mice overexpressing an adipocyte-specific, dominant-negative form of RhoA (DN-RhoA TG mice) showed decreased Rho-kinase activity in adipocytes, decreased HFD-induced weight gain, and improved glucose metabolism compared to wild-type littermates. (sciencemag.org)
- Although over-activation of the small G protein RhoA and its effector Rho kinase is recognized as a critical component of the pathogenesis of hypertension in experimental models and in human, the molecular mechanisms and the RhoA-GEF(s) involved in this activation of RhoA signaling in vascular smooth muscle cells (VSMCs) are still unknown. (ahajournals.org)
- Here we identify the RhoA-GEF and the molecular mechanism responsible for the activation of RhoA and Rho kinase in response to Ang II type 1 receptor activation (AT1R) in rat aortic VSMCs. (ahajournals.org)
- Systematic functional analysis by siRNA-mediated silencing of the 28 RhoA GEFs indicated that only Arhgef1 (p115, lsc) is involved in Ang II (0.1 μ M)-mediated RhoA/Rho kinase activation. (ahajournals.org)
- Knock-down of Arhgef1 had no significant effect on the activation of RhoA/Rho kinase induced by the thromboxan analog U46619, endothelin-1 and noradrenaline. (ahajournals.org)
- Ang II-induced Arhgef1 activation was further confirmed by in vitro guanine nucleotide exchange assay on RhoA, and we demonstrated by the transfection of Arhgef1 mutants that Ang II-induced Arhgef1 activation was due to its phosphorylation on Tyr738 by the tyrosine kinase Jak2. (ahajournals.org)
- Chronic infusion of Ang II (250 ng/kg/min, 14 days) through an osmotic minipump induced an increase in arterial pressure associated with enhanced RhoA/Rho kinase activity and activation of Arhgef1 in arteries. (ahajournals.org)
- 3, 4 The mechanisms underlying Ca 2+ sensitisation have not been fully elucidated, but RhoA, a small GTPase in the ras superfamily, and its target Rho associated kinase are involved in this process. (bmj.com)
- 11 Blocking RhoA signalling through Rho kinase would therefore be expected to attenuate contractile responses via the inhibition of the Ca 2+ sensitising mechanism. (bmj.com)
- Of direct relevance to the report of Wolfrum and coworkers 1 is our recent demonstration in BS/GS patients that RhoA/Rho Kinase pathway is blunted 6 and that the expression of p22 phox , a subunit of the multienzymatic complex NADPH oxidase, is reduced. (ahajournals.org)
- Sustained inhibition of the RhoA/Rho-kinase pathway throughout the period of hypoxic exposure attenuated PH and prevented remodeling in intra-acinar vessels without enlarging the structurally determined lumen diameter. (ahajournals.org)
- The small G-protein RhoA and its downstream effector Rho-kinase (ROCK) play a central role in diverse cellular functions including smooth muscle contraction, cytoskeletal rearrangement, cell migration, cell proliferation, and gene expression. (ahajournals.org)
- In parallel, dominant-negative RhoA (N19RhoA) and Y27632, a specific inhibitor of Rho-associated kinase, dramatically reverse the rounded cell morphology to a spread cell shape and enhance motility. (aacrjournals.org)
- Rho-associated coiled-coil kinase (ROCK) is a major downstream effector of the small GTPase RhoA. (iupui.edu)
- The small GTPase RhoA and its downstream effector, Rho kinase (ROCK), appear to mediate numerous pathophysiological signals, including smooth muscle cell contraction, actin cytoskeleton organization, cell adhesion and motility, proliferation, differentiation and the expression of several genes. (eurekaselect.com)
- Activated RhoA has recently been reported to interact directly with several protein kinases, p120 PKN, p150 ROK alpha and -beta, p160 ROCK, and p164 Rho kinase. (pubmedcentralcanada.ca)
- Hill CS, Wynne J, Treisman R. The Rho family GTPases RhoA, Rac1, and CDC42Hs regulate transcriptional activation by SRF. (pubmedcentralcanada.ca)
- We tested the role of the RhoA/Rho-associated kinase (ROCK) pathway, a TGFbeta-dependent pathway known to regulate cell migration. (cnrs.fr)
- Objective: The RhoA/Rho kinase pathway plays a pivotal role in cold-induced vasoconstriction, vascular smooth muscle cells function, and vascular homeostasis. (elsevier.com)
- The electrophysiological activity of Kv1.2 undergoes tyrosine kinase-dependent suppression in a process involving RhoA. (uvm.edu)
- Activation of RhoA downstream effectors Rho-kinase (ROCK) or protein kinase N (PKN) via the lysophosphatidic acid (LPA) receptor elicits clathrin-dependent Kv1.2 endocytosis and consequent attenuation of its ionic current. (uvm.edu)
- Both receptor-stimulated and steady-state Kv1.2 trafficking modulated by RhoA/ROCK require the activation of dynamin as well as the ROCK effector LIM kinase, indicating a key role for actin remodeling in RhoA-dependent Kv1.2 regulation. (uvm.edu)
- Rho-kinase inhibitors (rho-associated protein kinase inhibitor or ROCK inhibitor) are a series of compounds that target rho kinase (ROCK) and inhibit the ROCK pathway. (wikipedia.org)
- Rho/Rho-kinase pathway contributes to C-reactive protein-induced plasminogen activator inhibitor-1 expression in endothelial cells," Arteriosclerosis, Thrombosis, and Vascular Biology , vol. 25, no. 10, pp. 2088-2093, 2005. (hindawi.com)
- The effect of hCLOCK on the hypoxic response was evaluated with the use of a retroviral shRNA vector system, a Rho inhibitor, and a ROS scavenger by analyzing expression levels of hCLOCK, Rho GTPases, and NF- κ B pathway effectors. (hindawi.com)
- Rho kinase inhibitors have been shown to reduce IOP in rabbits and monkeys by increasing aqueous humor drainage through the primary outflow pathway in the eye, the trabecular meshwork. (aao.org)
- The Rho-kinase signaling pathway is substantially involved in vascular contraction. (mdpi.com)
- These findings suggested that DL0805 is a novel vasorelaxant compound associated with inhibition of Rho/ROCK signaling pathway. (mdpi.com)
- We have found that ROCK1, a Rho activated kinase, plays a key role in activating the intrinsic cell death pathway in response to genotoxic stress caused by UV or CPT. (aacrjournals.org)
- Furthermore, we have revealed that ROCK1-mediated activation of JNK kinase pathway functions through its interaction with the scaffolding protein JIP3. (aacrjournals.org)
- The principal determinant of smooth muscle contraction is the intracellular free Ca(2+) concentration, and phosphorylation of myosin light chain (MLC) by activated myosin light chain kinase (MLCK) in response to increased Ca(2+) is the main pathway by which vasoconstrictor stimuli induce crossbridge cycling of myosin and actin filaments. (medworm.com)
- Accumulating evidence has demonstrated that Rho/Rho-kinase pathway plays an important role in various cellular functions, not only in vascular smooth muscle cell (VSMC) contraction but also in actin cytoskeleton organization, cell adhesion and motility, cytokinesis, and gene expressions, all of which may be involved in the pathogenesis of cardiovascular disease. (ahajournals.org)
- The expression of Rho-kinase itself is mediated by protein kinase C/NF-κB pathway with an inhibitory and stimulatory modulation by estrogen and nicotine, respectively. (ahajournals.org)
- Role of Rho/Rho-kinase pathway in the pathogenesis of cardiovascular diseases. (ahajournals.org)
- Rho/Rho-kinase-mediated pathway plays an important role in the signal transduction initiated by many agonists, including angiotensin II (Ang II), serotonin (5-HT), thrombin, endothelin-1 (ET-1), norepinephrine (NE), platelet-derived growth factor (PDGF), adenosine triphosphate (ATP)/adenosine diphosphate (ADP), and urotensin II (Uro II). (ahajournals.org)
- It has been shown that the inhibition of the Rho/Rho kinase (ROCK) pathway prevents tubulointerstitial fibrosis and ameliorates renal function in various progressive renal disorders. (aspetjournals.org)
- These results suggest that inhibition of the Rho/ROCK pathway attenuates CsA-induced nephropathy through the suppression of the induction of inflammatory, apoptotic, and fibrogenic factors, along with inhibition of Smad, mitogen-activated protein kinases, and nitric oxide signaling pathways. (aspetjournals.org)
- Propofol uses the rho and rho kinase pathway to reorganize the actin cytoskeleton into ring structures, which is also dependent on a tyresine klnase. (diva-portal.org)
- In conclusion, diabetes-associated IPAs dysfunction involves increased NOX-1 derived ROS, decreased expression of Nrf2-regulated enzymes and activation of the Rho kinase pathway. (ahajournals.org)
- With the recent development of a specific Rho-kinase inhibitor such as Y-27632 and fasudil, the understanding of the role of the Rho/Rho-kinase pathway in vitro and in vivo has advanced. (nii.ac.jp)
- However, there have been few studies investigating the role of the Rho/Rho-kinase pathway in hypertensive glomerular sclerosis. (nii.ac.jp)
- In this review, we described the role of the Rho/Rho-kinase pathway in the progression of renal glomerulosclerosis in several forms of hypertensive rats. (nii.ac.jp)
- Our results suggest that chronic inhibition of the Rho-kinase pathway may be a new therapeutic approach for hypertensive glomerulosclerosis. (nii.ac.jp)
- These results suggest that the signalling pathway mediated through Rho kinase may have an important role in bronchial smooth muscle tone in allergen induced and virus induced AHR and should be considered as a novel target for asthma treatment. (bmj.com)
- In a recent article, Wolfrum et al 1 have shown that in human cells in culture, inhibition of Rho kinase (RKO) activates Akt pathway, which they contend leads to cardiovascular protection via activation of eNOS. (ahajournals.org)
- The Rho-associated kinase (ROCK) signaling pathway has recently been extensively studied due to its importance in a myriad of disease states. (arvojournals.org)
- Our results suggest that R-Ras in breast epithelial cells disrupts cell polarity and motility through the Rho/Rho-associated kinase pathway triggered by a signal from the COOH-terminal end of R-Ras. (aacrjournals.org)
- The ROCK inhibitor Y27632 completely inhibited ET-1-promoted contraction and the phosphatase inhibitor calyculin elicited contraction in the absence of any other agonists, suggesting that activation of the Rho/ROCK/myosn light chain phosphatase pathway is critical in regulating in vivo myofibroblast contraction. (epfl.ch)
- These results are consistent with inhibition of myosin light chain phosphatase by the Rho/ROCK signaling pathway, which would account for the long-duration contraction of myofibroblasts necessary for wound closure. (epfl.ch)
- Activation of the MAP kinase pathway by the protein kinase raf. (pubmedcentralcanada.ca)
- Objectives This study examined whether the Rho-kinase pathway is involved in the pathogenesis of coronary hyperconstricting responses induced by drug-eluting stents (DES) in pigs in vivo. (onlinejacc.org)
- We have previously shown that the activated Rho-kinase pathway plays a central role in the molecular mechanism of coronary vasospasm in animals and humans. (onlinejacc.org)
- Conclusions These results suggest that the Rho-kinase pathway plays an important role in the pathogenesis of DES-induced coronary hyperconstricting responses. (onlinejacc.org)
- In summary we describe a pathway involving PI3K/Rho/ROCK/MLC that may contribute to myeloproliferative disease and/or acute myeloid leukemia in humans. (luriechildrens.org)
- AMP-activated protein kinase (AMPK) and Rho kinase (ROK) are known to modulate the mevalonate pathway. (semanticscholar.org)
- On the other hand, it has been shown that the rho/rho kinase pathway is involved in mechanisms of several aspects such as endothelial cell dysfunction and apoptosis. (biomedcentral.com)
- RHO signalling is a cell signalling pathway by which extracellular or intracellular stimuli promote activation of the small GTPase RHO. (nature.com)
- There is increasing evidence that the Rho/ROCK (Rho kinase) signalling pathway may play a critical role in the inflammatory response, and ROCK inhibitor has been reported to have neuroprotective effects. (readbyqxmd.com)
- Rho-kinase inhibitors as therapeutics: from pan inhibition to isoform selectivity. (ebi.ac.uk)
- Some studies suggest that Rho kinase inhibitors also play a role in anti-angiogenesis by blocking ERK and Akt signaling pathways. (wikipedia.org)
- A number of Rho kinase inhibitors are known. (wikipedia.org)
- Rho kinase inhibitors block melanoma cell migration and inhibit metastasis. (sigmaaldrich.com)
- Fragment-based screening has led to the discovery of orally available, ATP-competitive AKT kinase inhibitors, AT13148 and CCT129254. (sigmaaldrich.com)
- Small-molecule kinase inhibitors are predominantly discovered in pure protein assays. (nih.gov)
- Rockout inhibits blebbing and causes dissolution of actin stress fibers, phenocopying Rho-kinase inhibitors. (nih.gov)
- In this study, we have employed many techniques such as short hairpin RNA to knockdown gene expression, chemical inhibitors to inhibit kinase activities, flow cytometery analysis, cell death assay, confocal microscopy to visualize actin staining and co-immunoprecipitaion to verify protein interactions. (aacrjournals.org)
- Genetically induced loss of RHO function impedes transformation by a number of oncogenic stimuli, leading to an interest in developing small-molecule inhibitors that either target RHO GTPases directly, or that target their downstream protein kinase effectors. (aacrjournals.org)
- Although inhibitors of RHO GTPases and their downstream signaling kinases have not yet been widely adopted for clinical use, their potential value as cancer therapeutics continues to facilitate pharmaceutical research and development and is a promising therapeutic strategy. (aacrjournals.org)
- As with RAS, the RHO GTPases have proven difficult to target directly with small-molecule inhibitors. (aacrjournals.org)
- While efforts continue to develop direct small GTPase inhibitors, a promising and more conventional therapeutic approach has been to block the activities of RHO GTPase effectors. (aacrjournals.org)
- For example, RAC and CDC42 share two protein serine-threonine kinase effectors in common, PAK and MLK, and inhibitors for both these kinases have been developed. (aacrjournals.org)
- Intraperitoneal pretreatment with the selective Rho-kinase inhibitors fasudil (4â€"40 mg/kg) and Y-27632 (1â€"10 mg/kg) was administered prior to induction of colonic I/R. Leukocyteâ€"endothelium interactions were analyzed by intravital fluorescence microscopy. (ebscohost.com)
- Westem blotting (WB) was used to visualize tyresine phosphorylated immunoprecipitated proteins and changes in actin between the different cellularcompartments after inhibition with rho (C 3 exotoxin) and rho kinase (ROK) (HA-1077) inhibitors. (diva-portal.org)
- Pretreatment of the cells with Botulinum C3 ADP-ribosyltransferase (C3), which is thought to interfere with Rho functions, or Rho-kinase inhibitors inhibited the TPA- or HGF-induced MBS phosphorylation. (nih.gov)
- The present disclosure describes peptide inhibitors of Rho-associtated-kinase (ROCK) and their use in treating disorders including heart failure, the leading cause of combined morbidity and mortality in the United States. (wipo.int)
- Hong Zhou and Yong-jun Li, "Rho Kinase Inhibitors: Potential Treatments for Diabetes and Diabetic Complications", Current Pharmaceutical Design (2012) 18: 2964. (eurekaselect.com)
- It has recently been shown that Rho kinase (ROCK) activation is involved in many neurodegenerative diseases, and some ROCK inhibitors might promote the degradation of abnormal protein aggregates. (readbyqxmd.com)
-  This invention relates to substituted amide derivatives which are useful as inhibitors of Rho kinase and are thus useful for treating a variety of diseases and disorders that are mediated or sustained through the activity of Rho kinase, including cardiovascular diseases, cancer, neurological diseases, renal diseases, bronchial asthma, erectile dysfunction, and glaucoma. (patentsencyclopedia.com)
- Rho-associated protein kinases (ROCKs) were originally identified as small GTPase Rho effectors. (ebi.ac.uk)
- ROCK plays a role in a wide range of different cellular phenomena, as ROCK is a downstream effector protein of the small GTPase Rho, which is one of the major regulators of the cytoskeleton. (wikipedia.org)
- The small guanosine triphosphatase (GTPase) Rho is implicated in the formation of stress fibers and focal adhesions in fibroblasts stimulated by extracellular signals such as lysophosphatidic acid (LPA). (sciencemag.org)
- The small GTPase Rho is inactive in its guanosine diphosphate (GDP)-bound form and active in its guanosine triphosphate (GTP)-bound form ( 1 ). (sciencemag.org)
- Upon UV irradiation or CPT treatments of the cells, ROCK1 is activated by small GTPase Rho and caspase-3 cleavage. (aacrjournals.org)
- Thus, the Mst1 and Mst2 kinases control Rho GTPase activation and the migratory responses of SP thymocytes. (rupress.org)
- Rho-associated kinase (Rho-kinase), which is activated by the small GTPase Rho, phosphorylates myosin-binding subunit (MBS) of myosin phosphatase and thereby inactivates the phosphatase activity in vitro. (nih.gov)
- The small GTPase Rho is suggested as a crucial regulator in these processes of cytokinesis. (biologists.org)
- Rho-associated kinase (Rho-kinase), which is activated by the small GTPase Rho, regulates formation of stress fibers and focal adhesions, myosin fiber organization, and neurite retraction through the phosphorylation of cytoskeletal proteins, including myosin light chain, the ERM family proteins (ezrin, radixin, and moesin) and adducin. (rupress.org)
- Like Ras, the Rho proteins (which include Rho, Rac, and CDC42) interact directly with protein kinases, which are likely to serve as downstream effector targets of the activated GTPase. (pubmedcentralcanada.ca)
- The association of p140 with either GTPase promotes kinase activity substantially, and expression of a kinase-deficient form of p140 in microinjected fibroblasts disrupts actin stress fibers. (pubmedcentralcanada.ca)
- The Ras GTPase-activating-protein-related human protein IQGAP2 harbors a potential actin binding domain and interacts with calmodulin and Rho family GTPases. (pubmedcentralcanada.ca)
- We show constitutive activation of Rho kinase (ROCK) in cells bearing oncogenic forms of KIT, FLT3, and BCR-ABL, which is dependent on PI3K and Rho GTPase. (luriechildrens.org)
- GTPase family member Rho kinase, have been identified as capable of phosphorylating the C-terminal threonine. (edu.au)
- The Rho family GTPase Cdc42 regulates the activation of Ras/MAP kinase by the exchange factor Ras-GRF. (hud.ac.uk)
- In an unprecedented fashion, we have found that these processes are regulated by the Rho family GTPase Cdc42. (hud.ac.uk)
- Indeed, cells can use different migrational modes to move with varying degrees of speed and directionality depending on the nature of Rho GTPase signaling downstream of integrins. (rupress.org)
- They find that dissociation of the RhoGDIα-Rho GTPase complex is increased by shear stress and varies with subcellular location. (nature.com)
- Rho GTPase regulation of α-synuclein and VMAT2: implications for pathogenesis of Parkinson's disease. (readbyqxmd.com)
- Plant RHO GTPases (RAC/ROPs) mediate multiple extracellular signals ranging from hormone to stress and regulate diverse cellular processes important for polarized cell growth, differentiation, development, reproduction, and responses to the environment. (pnas.org)
- RHO GTPases are a large family of related monomeric GTP-binding proteins that serve diverse signaling functions ( 1 ). (pnas.org)
- Plant RAC/ROPs form a unique clade of RHO-like GTPases and play important roles in regulating cell growth and polarity establishment, hormone- and stress-induced responses that underlie growth, development, reproduction, and interactions with the environment ( 2 - 4 ). (pnas.org)
- Expression levels of Rho GTPases were measured in normoxic and hypoxic states. (hindawi.com)
- Rho family GTPases have received increasing attention as critical regulators of cell function ( 1 ). (diabetesjournals.org)
- Rho GTPases, a family of small GTP-binding proteins, are important candidates to coordinate remodeling of the actin cytoskeleton during myelination. (jneurosci.org)
- Rho GTPases are molecular switches, cycling between an inactive (GDP-bound) and an active (GTP-bound) state. (jneurosci.org)
- RHO GTPases, members of the RAS superfamily of small GTPases, are adhesion and growth factor-activated molecular switches that play important roles in tumor development and progression. (aacrjournals.org)
- Signaling from RHO-family GTPases. (aacrjournals.org)
- The three major RHO-family GTPases, CDC42, RAC, and RHO, are activated by guanine-nucleotide exchange factors (GEF), which are in turn regulated by signals originating at the cell surface. (aacrjournals.org)
- The TJ, a multifunctional complex, and its regulation by Rho GTPases, are often overlooked in mediating endothelial renewal. (molvis.org)
- Small Rho-GTPases are enzymes that are bound to GDP or GTP which Imatinib determines their energetic or inactive state respectively. (exposed-skin-care.net)
- The PRK2 kinase is a potential effector target of both Rho and Rac GTPases and regulates actin cytoskeletal organization. (pubmedcentralcanada.ca)
- The Ras-related Rho family GTPases mediate signal transduction pathways that regulate a variety of cellular processes. (pubmedcentralcanada.ca)
- These results indicate that p140 may be a shared kinase target of both Rho and Rac GTPases that mediates their effects on rearrangements of the actin cytoskeleton. (pubmedcentralcanada.ca)
- A Rho inhibitor, ML141, LY294002, and an Akt1/2 inhibitor diminished K. pneumoniae invasion in a dose-dependent manner, indicating that Rho family GTPases and phosphatidylinositol 3-kinase (PI3K)/Akt signaling were required. (asm.org)
- Modular regulation of Rho family GTPases in development. (semanticscholar.org)
- Functions of Rho family of small GTPases and Rho-associated coiled-coil kinases in bone cells during differentiation and mineralization. (semanticscholar.org)
- The Ras guanine-nucleotide exchange factor Ras-GRF/Cdc25(Mn) harbors a complex array of structural motifs that include a Dbl-homology (DH) domain, usually found in proteins that interact functionally with the Rho family GTPases, and the role of which is not yet fully understood. (hud.ac.uk)
- As downstream effectors of Rho GTPases, their major substrates are myosin light chain and myosin phosphatase. (rupress.org)
- Small Rho GTPases are molecular switches that control actin cytoskeleton organization, cell adhesion and migration, gene expression, microtubule dynamics, and vesicle transport ( Etienne-Manneville and Hall, 2002 ). (rupress.org)
- present a new FRET biosensor for measuring the spatio-temporal activation of RhoGDIα upon binding Rho GTPases. (nature.com)
- AT-13148 BA-210 β-Elemene DJ4, which is a selective multi-specific ATP competitive inhibitor of activity of ROCK1 (IC50 of 5 nM), ROCK2 (IC50 of 50 nM), MRCKα (IC50 of 10 nM) and MRCKβ (IC50 of 100 nM) kinases without affecting activity of PAK1 and DMPK at 5 μM concentrations in in vitro cell-free kinase activity assays. (wikipedia.org)
- The grant provides funding for milestone-driven research to assess the potential of BA-1049, a Rho Kinase 2 (ROCK2) inhibitor in BioAxone's pipeline, to improve recovery in chronic spinal cord injury. (news-medical.net)
- 5m grant, the third year installment to continued research into BioAxone's first-in-class selective Rho Kinase 2 (ROCK2) inhibitor, BA-1049, a drug in development to treat cerebral cavernous malformations (CCM), the company said. (thefreedictionary.com)
- In preclinical experiments BA-1049, a first-in-class oral inhibitor of Rho kinase 2 (ROCK2), has shown promise to repair the leaky endothelial cell barrier and potentially to reverse progression of disease. (thefreedictionary.com)
- US-based biotechnology company BioAxone BioSciences, Inc has entered a contract with US-based Wilmington PharmaTech to manufacture the company's BA-1049, a selective inhibitor of Rho kinase 2 (ROCK2), the company said. (thefreedictionary.com)
- Here, we report that protein levels of the Rho-associated protein kinases (ROCK1 and ROCK2), p70 S6 kinase (S6K), and mammalian target of rapamycin (mTOR) were increased in PSP and CBD brains. (jneurosci.org)
- In this report, the Rho-associated protein kinases (ROCK1 and ROCK2) are identified as novel drug targets for PSP and CBD. (jneurosci.org)
- ROCK2 is a 160 kDa serine/threonine kinase which is composed of a kinase domain (44-415 aa) at the amino-terminus, a rho-binding domain (981-1046 aa), and a pleckstrin homology (PH) domain with a cysteine-rich region at the carboxyl-terminus (1152-1350 aa). (atlasgeneticsoncology.org)
- Kinase domain of ROCK2 is the key domain conferring the most important function of ROCK2 which is the phosphorylation and activation of its downstream substrates (Leung et al. (atlasgeneticsoncology.org)
- 1999). The ROCK2 kinase domain can also be released when the C-terminus of ROCK2 is cleaved by granzyme B (Sebbagh et al. (atlasgeneticsoncology.org)
- 2005). Furthermore, Polo-like kinase-1 (Plk1) interacts with and phosphorylates ROCK2 at Threonine 967, Serine 1099, Serine 1133, and S1374 and activates ROCK2 (Lowery et al. (atlasgeneticsoncology.org)
- In mid 1990s, 2 Japanese groups and 1 Singapore group independently identified one of the effectors of Rho and termed it as Rho-kinase α 3 /ROKα 4 /ROCK2. (ahajournals.org)
- Hereafter, both Rho-kinase α/ROKα/ROCK2 and Rho-kinase β/ROKβ/ROCK1 are collectively referred to as Rho-kinase. (ahajournals.org)
- Rho-kinase is one of the down-stream effectors of the small GTP-binding protein Rho and consists of 2 isoforms, Rho-kinase beta (ROCK1) and Rho-kinase alpha (ROCK2) ( 11,12 ). (onlinejacc.org)
- The aim of this study was to investigate the association between Rho-kinase (ROCK2) gene polymorphisms and patients with BD in a Turkish population. (behcet.es)
- Rho Associated Protein Kinase 2 (Rho Kinase 2 or Rho Associated Coiled Coil Containing Protein Kinase 2 or p164 ROCK 2 or ROCK2 or EC 188.8.131.52) - Pipeline Review, H1 2018 report is published on February 27, 2018 and has 62 pages in it. (marketresearchreports.com)
- The latest report Rho Associated Protein Kinase 2 - Pipeline Review, H1 2018, outlays comprehensive information on the Rho Associated Protein Kinase 2 (Rho Kinase 2 or Rho Associated Coiled Coil Containing Protein Kinase 2 or p164 ROCK 2 or ROCK2 or EC 184.108.40.206) targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (marketresearchreports.com)
Role of Rho kinase6
- Because of its key role as a regulator of the cytoskeleton, we investigated the role of Rho kinase (ROCK), a major downstream effector of Rho, in Schwann cell morphology, differentiation, and myelination. (jneurosci.org)
- The role of Rho kinase in Ca 2+ sensitization of the contractile apparatus in smooth muscle was investigated in the bovine middle cerebral artery. (wiley.com)
- Rho-Mancing to Sensitize Calcium Signaling for Contraction in the Vasculature: Role of Rho Kinase. (medworm.com)
- However, to date, there have been few studies investigating the role of Rho-kinase in renal disease. (nii.ac.jp)
- In these experiments we have investigated specifically the potential role of Rho kinase mediated ERM activation in cortical neurons, utilizing a new pharmacologic inhibitor of Rho kinase and quantitative analysis of aspects of neuronal functions potentially mediated by ERM proteins. (edu.au)
- However, the role of rho kinase in the concept of sepsis-induced apoptosis has yet to be elucidated. (biomedcentral.com)
- Rat ROCKs were discovered as the first effectors of Rho and they induce the formation of stress fibers and focal adhesions by phosphorylating MLC (myosin light chain). (wikipedia.org)
- Rho-kinase has been identified as one of the effectors of the small GTP-binding protein Rho. (ahajournals.org)
- In addition to Rho-kinase, several other proteins have been identified as effectors of Rho, including protein kinase N (PKN), rhophilin, rhotekin, citron, p140mDia, and citron kinase 6,7 ( Figure 1 ). (ahajournals.org)
- However, the roles of those effectors of Rho other than Rho-kinase remain to be examined. (ahajournals.org)
- Through the modulation of its target effectors, Rho-kinase is substantially involved in the vascular smooth muscle contraction (via inhibition of myosin phosphatase) and in the pathogenesis of arteriosclerosis (via activation of ERM, adducin, and other effectors). (ahajournals.org)
- Among these effectors are several protein kinases that either are or might be amenable to small-molecule inhibition ( Fig. 1 ). (aacrjournals.org)
- CDC42 also has distinct kinase effectors, such as MRCK and the tyrosine kinase ACK, and these kinases too might provide suitable drug targets in cancer. (aacrjournals.org)
- Among the Rho effectors, the cellular function and signal transduction of Rho-kinase have been extensively studied. (nii.ac.jp)
- Rac also has multiple effectors, one of which is the serine threonine kinase Pak (p65 Pak ). (asm.org)
- Although these studies suggest that the signal from Ras through PI 3-kinase is sufficient to activate Pak, additional studies suggested that other effectors contribute to Pak activation. (asm.org)
- These data suggest that other Ras effectors can collaborate with PI 3-kinase and with each other to activate Pak. (asm.org)
- The three effectors that have been most widely studied are Rin, Ral GDS, and phosphoinositide 3-OH kinase (PI 3-kinase) ( 1 , 39 , 46 ). (asm.org)
- Rho-kinases are downstream effectors of Rho guanosine triphosphatases in the regulation of cytoskeletal reorganization and cell motility. (hku.hk)
- Two homologous serine/threonine kinases (ROCK I and II, also known as ROKβ and α, respectively) are major Rho effectors and are implicated in the formation of stress fibers and focal adhesions in nonmuscle cells, contractility of smooth muscle, and suppression of neurite outgrowth ( Riento and Ridley, 2003 ). (rupress.org)
- Cell adhesion, mechanical stress and membrane receptor signalling activate RHO, which signals through effectors to promote changes in cell adhesion and contractility, gene expression, cell division and proliferation, and other effects. (nature.com)
- Hypoxia-induced MLC phosphorylation was inhibited by Y-27632 (a Rho-kinase inhibitor), exoenzyme C3 (a specific Rho inhibitor), or toxin B (an inhibitor for Rho proteins). (nih.gov)
- In summary, the data show that Rho-kinase is activated by hypoxia in PASMCs, and Rho/Rho-kinase is functionally linked to hypoxia-induced MLC phosphorylation and plays a role in the sustained phase of HPV. (nih.gov)
- These results support a key role of Rho through its effector ROCK in coordinating the movement of the glial membrane around the axon at the onset of myelination via regulation of myosin phosphorylation and actomyosin assembly. (jneurosci.org)
- The small guanosine triphosphatase Rho is implicated in myosin light chain (MLC) phosphorylation, which results in contraction of smooth muscle and interaction of actin and myosin in nonmuscle cells. (nih.gov)
- Induction of intrinsic cell death (through disruption of mitochondrial integrity) is very often accompanied by the activation of the stress activated MAPK kinase, JNK which, through the phosphorylation of Bcl-2 and Bcl-XL, results in fatal mitochondrial cytochrome C release. (aacrjournals.org)
- Our results elucidated the key role of ROCK1 in mediating the apoptotic signals from Rho and caspase-3 to JNK phosphorylation through interaction with JIP3 protein. (aacrjournals.org)
- During the steady state of the U46619-induced contraction, Y27632 (10 μ M ), a Rho-kinase inhibitor, partially inhibited [Ca 2+ ] i , although it substantially inhibited tension and MLC phosphorylation. (wiley.com)
- Wortmannin (10 μ M ), an MLC kinase inhibitor, had no significant effect on [Ca 2+ ] i , but it completely inhibited MLC phosphorylation and partially inhibited tension. (wiley.com)
- It was subsequently demonstrated that Rho-kinase enhances myosin light chain (MLC) phosphorylation through inhibition of MBS of myosin phosphatase 8,9 ( Figure 1 ). (ahajournals.org)
- In another series of experiments using HK-2 cells in culture, fasudil also suppressed CsA-induced increases in mitogen-activated protein kinase phosphorylation. (aspetjournals.org)
- Phosphorylation of myosin-binding subunit (MBS) of myosin phosphatase by Rho-kinase in vivo. (nih.gov)
- Rho-kinase is thought to regulate the phosphorylation state of the substrates including myosin light chain (MLC), ERM (ezrin/radixin/moesin) family proteins and adducin by their direct phosphorylation and by the inactivation of myosin phosphatase. (nih.gov)
- Here we identified the sites of phosphorylation of MBS by Rho-kinase as Thr-697, Ser-854 and several residues, and prepared antibody that specifically recognized MBS phosphorylated at Ser-854. (nih.gov)
- Taken together, these results indicate that MBS is phosphorylated by Rho-kinase downstream of Rho in vivo, and suggest that myosin phosphatase and Rho-kinase spatiotemporally regulate the phosphorylation state of Rho-kinase substrates including MLC and ERM family proteins in vivo in a cooperative manner. (nih.gov)
- Rho- and Rho-kinase-dependent phosphorylation of MBS at Ser-854 in MDCK cells. (nih.gov)
- 5- 7 Rho associated coiled coil-forming protein kinase (ROCK I) and its isoform ROCK II 8- 10 inhibit MLCP activity and promote the activity of MLCK, thereby increasing the level of MLC phosphorylation and increasing muscular tension. (bmj.com)
- In this report, we show that constitutively active R-Ras (38V) induces a more rounded cell shape and redistribution of focal adhesion, and enhances the phosphorylation of focal adhesion kinase and paxillin. (aacrjournals.org)
- Medley and colleagues showed the kinase website of Trio known to interact with LAR is definitely constitutively phosphorylated Imatinib on tyrosine residues.6 The levels of phosphorylation were further increased when FAK was co-expressed. (exposed-skin-care.net)
- We then constructed a series of mutant GFAPs, where Rho-kinase phosphorylation sites were variously mutated, and expressed them in type III IF-negative cells. (rupress.org)
- Alteration of other sites, including the cdc2 kinase phosphorylation site, led to no remarkable defect in glial filament separation. (rupress.org)
- We examined whether regulation of myofibroblast contraction in granulation tissue is dominated by Ca2+-induced phosphorylation of myosin light chain kinase or by Rho/Rho kinase (ROCK)-mediated inhibition of myosin light chain phosphatase, similar to that of cultured myofibroblasts. (epfl.ch)
- Rho-associated kinase directly induces smooth muscle contraction through myosin light chain phosphorylation. (semanticscholar.org)
- Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase). (semanticscholar.org)
- Importantly, inhibition of Rho kinase, either by Y27632 or RNA interference, resulted in inhibition of Thr567 phosphorylation and a blockade to cell invasion, implicating Rho kinase-ezrin signaling in hepatocellular carcinoma cell invasion. (northwestern.edu)
- Our findings suggest a strategy to reduce liver tumor metastasis by blocking Rho kinase-mediated phosphorylation of ezrin. (northwestern.edu)
- Target proteins, the functions of which are modulated by Rho, include protein kinase N (PKN) ( 9 ), Rho-kinase ( 10 ) [also called Rho-binding kinase ( 11 )], and the myosin-binding subunit (MBS) of myosin phosphatase ( 12 ). (sciencemag.org)
- We produced four fragments containing these domains as glutathione-S-transferase (GST) fusion proteins: GST-CAT (catalytic domain, amino acids 6 to 553), GST-COIL (coiled-coil domain, amino acids 421 to 701), GST-RB (Rho-binding domain, amino acids 941 to 1075), and GST-PH (pleckstrin-homology domain, amino acids 1125 to 1388). (sciencemag.org)
- Recent advances in molecular biology have elucidated the substantial involvement of intracellular signaling pathways mediated by small GTP-binding proteins (G proteins), such as Rho, Ras, Rab, Sarl/Arf, and Ran families. (ahajournals.org)
- Whereas statins inhibit Rho at their relatively higher concentrations, they simultaneously inhibit pathways mediated by other G proteins, such as Ras and Rac. (ahajournals.org)
- Upon activation, RHO proteins recruit and activate a number of cytoplasmic protein kinases, indicated in green. (aacrjournals.org)
- These protein kinases in turn regulate the activities of a number of additional effector proteins, including those that modulate cell proliferation, survival, and migration. (aacrjournals.org)
- p21-activated kinases (PAK), the most extensively studied CDC42 and RAC effector proteins, consist of two subgroups containing three members each: group I (PAK1-3) and group II (PAK4-6). (aacrjournals.org)
- Among the GTP-binding proteins, Rho is known to function as a molecular switch in various cellular functions. (nii.ac.jp)
- Internalization of the podocyte slit membrane proteins nephrin and synaptopodin was prevented by Rho-kinase inhibition. (uzh.ch)
- Keywords: Trio Rac1 RhoG lamellipodia Rho-GEF Launch The Rho-GEF Trio was originally discovered in 1996 being a binding partner from the transmembrane tyrosine phosphatase LAR.1 Trio is a big proteins of 350 kD that harbors three domains with putative enzymatic activity hence the name Trio. (exposed-skin-care.net)
- Ras V12S35 and Ras V12G37 , two effector mutant proteins which fail to activate PI 3-kinase, did not activate Pak when tested alone but activated Pak when they were cotransfected. (asm.org)
- Rho and two related proteins, Rac and Cdc42, are members of the Rho family of small G proteins. (asm.org)
- All Shroom proteins tested to date bind to both F-actin and Rho-associated kinase (Rock) via signature sequence motifs known as Shroom domain 1 (SD1) and 2 (SD2), respectively. (biologists.org)
- We were going to compare Rho/ROCK expression and eNOS expression/activity in carotid specimens obtained from patients treated with fasudil and compare those to specimens obtained from patients treated with placebo. (clinicaltrials.gov)
- We anticipated that Rho/ROCK expression and activity would be decreased in spcimens obtained from fasudil treated patients compared to specimens obtained from patients treated with placebo. (clinicaltrials.gov)
- Fasudil is a relatively specific ROCK inhibitor, although it also inhibits other kinases, including protein kinase C-related protein kinase and mitogen- and stress-activated protein kinase 1, with lower potency ( 10 ). (diabetesjournals.org)
- Treatment with the Rho-kinase inhibitor fasudil attenuated weight gain and insulin resistance in mice on a HFD. (sciencemag.org)
- Moreover, these findings show that Rho-kinase signalling regulates TNF-Î± and CXC chemokine formation as well as lipid peroxidation in the reperfused colon. (ebscohost.com)
- Numerous studies have shown that Shroom3 likely regulates these developmental processes by directly binding to Rho-kinase and facilitating the assembly of apically positioned contractile actomyosin networks. (biologists.org)
- These compounds also inhibit the Rho-kinases ROCK 1 and ROCK 2 and we show they potently inhibit ROCK activity in melanoma cells in culture and in vivo. (sigmaaldrich.com)
- Thus, Rho appears to inhibit myosin phosphatase through the action of Rho-kinase. (nih.gov)
- Second, given the potential for NO to inhibit vascular Rho-kinase function, we tested whether basal NOS activity in cerebral arteries in vivo is influenced by gender. (ahajournals.org)
- A recently developed pyridine derivative, Y-27632, a selective Rho kinase inhibitor, has been reported to inhibit the smooth muscle contraction of human and animal trachea in ex vivo systems but its effect in animal models of airway hyperresponsiveness (AHR) has not been examined. (bmj.com)
- The present invention provides compounds of formula (I) which inhibit the activity of PI 3-kinase gamma isoform, which are useful for the treatment of diseases. (patents.com)
- These substrates, once phosphorylated, regulate actin filament organization and contractility as follows: Amount of actin filaments ROCK inhibits the depolymerization of actin filaments indirectly: ROCK phosphorylates and activates LIM kinase, which in turn phosphorylates ADF/cofilin, thereby inactivating its actin-depolymerization activity. (wikipedia.org)
- Rho-kinase phosphorylates MBS and consequently inactivates myosin phosphatase ( 12 ). (sciencemag.org)
- Rho-kinase phosphorylates myosin light chain and thereby activates myosin adenosine triphosphatase (ATPase) ( 13 ). (sciencemag.org)
- Cdc42 and PAK-mediated signaling leads to Jun kinase and p38 mitogen-activated protein kinase activation. (pubmedcentralcanada.ca)
- Here, we present evidence that Ras-GRF requires its DH domain to translocate to the membrane, to stimulate exchange on Ras, and to activate mitogen-activated protein kinase (MAPK). (hud.ac.uk)
- K. D. Luykenaar, R. A. El-Rahman, and M. P. Walsh, "Rho-kinase-mediated suppression of KDR current in cerebral arteries requires an intact actin cytoskeleton," American Journal of Physiology-Heart and Circulatory Physiology , vol. 296, no. 4, pp. (hindawi.com)
- Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. (rcsb.org)
- Inhibitory signaling of myelin components and other repulsive guidance cues converges upon Rho-associated kinase (ROCK), which propagates this signal down to the cytoskeleton, influencing neurite growth and regeneration. (frontiersin.org)
- The activation eaused by propofol of rho and rho kinase causes actin to be moved from the cytoskeleton to the cell membrane and cytosol. (diva-portal.org)
- Since Rho kinase (ROCK) mediates cellular contraction through effects on the actin cytoskeleton and is an important regulator of cardiac fibrosis, we hypothesize that ACEi may improve heart function through inhibition of ROCK activity. (ahajournals.org)
- Rho-kinases play a central role in the organization of the actin cytoskeleton of podocytes. (uzh.ch)
- Similarly, in dividing cells, a structure composed of Rho and Citron-K in cleavage furrow excludes cortical actin cytoskeleton, and disruption of F-actin disperses Citron-K throughout the cell cortex. (biologists.org)
- Rho is then activated, binds to Citron-K and translocates it to cell cortex, where the complex is then concentrated in the cleavage furrow by the action of actin cytoskeleton beneath the equator of dividing cells. (biologists.org)
- Inhibiting Fgfr-Ras-MAPK leads to loss of apically localized Rho-associated kinase (Rock) 2a, which results in failed actomyosin cytoskeleton activation. (biologists.org)
- Rho-associated kinase 1 (ROCK1) is a serine/threonine kinase important for the regulation of the cellular cytoskeleton through the induction of actin stress fibres and acto-myosin contractility. (gla.ac.uk)
- Finally, I now demonstrate that the three nonsynonymous somatic mutations in the ROCK1 gene identified in the Cancer Genome Project lead to elevated kinase activity and drive actin cytoskeleton rearrangements that promote increased motility and decreased adhesion, characteristics of cancer progression. (gla.ac.uk)
- In addition, hypoxia-induced Rho-kinase activation was blocked by C3 and toxin B. Small rat intrapulmonary arterial rings, which were made hypoxic (PO(2) = 30 +/- 3 mm Hg), showed a slow sustained contraction, and Y-27632 caused a significant relaxation during the sustained phase of HPV in a concentration-dependent manner. (nih.gov)
- these calcium ions, in turn stimulate a myosin light chain kinase, forcing a contraction. (wikipedia.org)
- Rho also participates in the regulation of cell morphology ( 3 ), cell aggregation ( 4 ), cell motility ( 5 ), cytokinesis ( 6 ), and smooth muscle contraction ( 7 ). (sciencemag.org)
- In this review, we describe the molecular mechanisms underlying the pivotal role exerted by Rho kinase on vascular smooth muscle contraction and discuss the main regulatory pathways for its activity. (medworm.com)
- However, the relative contributions of these two kinases to vascular contraction, and whether their roles vary between large and small arteries, are largely unknown. (aspetjournals.org)
Phosphatidylinositol 3 kina1
- Inhibition of Rho-kinase leads to rapid activation of phosphatidylinositol 3 kinase/protein kinase Akt and cardiovascular protection. (ahajournals.org)
- Rho-associated coiled-coil kinase (ROCK) signaling and disease. (ebi.ac.uk)
- Decrease in Rho/ROCK Expression With Concordant Increase in eNOS Expression/Activity in Carotid Specimens. (clinicaltrials.gov)
- Increased leukocyte rho kinase (ROCK) activity and endothelial dysfunction in cigarette smokers," Hypertension Research , vol. 33, no. 4, pp. 354-359, 2010. (hindawi.com)
- Rho-associated protein kinase (ROCK) is a kinase belonging to the AGC (PKA/ PKG/PKC) family of serine-threonine kinases. (wikipedia.org)
- 1. ROCK is a key regulator of actin organization and thus a regulator of cell migration as follows: Different substrates can be phosphorylated by ROCKs, including LIM kinase, myosin light chain (MLC) and MLC phosphatase. (wikipedia.org)
- Thus in both cases, ROCK activation by Rho induces the formation of actin stress fibers, actin filament bundles of opposing polarity, containing myosin II, tropomyosin, caldesmon and MLC-kinase, and consequently of focal contacts, which are immature integrin-based adhesion points with the extracellular substrate. (wikipedia.org)
- The pro-apoptotic protease, caspase 3, activates ROCK kinase activity by cleaving the C-terminal PH domain. (wikipedia.org)
- Other targets of Rho with unknown functions include rhophilin, p160 Rho-associated coiled-coil-containing protein kinase (ROCK), rhotekin, citron ( 9 , 14 ), and phosphatidylinositol-4-phosphate 5-kinase (PIP5-K) ( 15 ). (sciencemag.org)
- We have discovered an inhibitor of Rho-kinase (ROCK) through an image-based, high-throughput screen of cell monolayer wound healing. (nih.gov)
- One key mediator of growth inhibitory signaling is Rho-associated kinase (ROCK), which has been shown to modulate growth cone stability by regulation of actin dynamics. (frontiersin.org)
- To assess the effects of Rho-associated kinase (ROCK) inhibition on the intraocular penetration of timolol maleate. (arvojournals.org)
- Aim To demonstrate the efficacy of Rho-associated kinase (ROCK) inhibitor Y-27632 for corneal endothelial wound healing both in in vitro and in vivo models. (bmj.com)
- The purpose of this study was to investigate the feasibility of using Rho-associated kinase (ROCK) inhibitor eye drops for treating severe corneal endothelial damage due to surgical invasion. (arvojournals.org)
- Rho-kinase (ROCK) activation in hepatic stellate cells (HSC) is a key mechanism promoting liver fibrosis and portal hypertension (PTH). (sdu.dk)
- Rho/Rho-kinase (ROCK) signaling contributes to neuroinflammation, epileptogenesis, and seizures in convulsive-type epilepsies. (springer.com)
- In summary, Rho/ROCK signaling may be involved in the pathophysiology of absence epilepsy. (springer.com)
- Interestingly, blocking ROCK with the chemical in-hibitor Y27632 had an effect opposite to TGF activation because it promoted superficial EVCT migration on the en-dometrial cell layer. (inserm.fr)
- In particular, inhibition of geranylgeranylpyrophosphate synthesis leads to inhibition of Rho and its downstream target, Rho-kinase (ROCK). (eurekaselect.com)
- The homologous mammalian rho kinases (ROCK I and II) are assumed to be functionally redundant, based largely on kinase construct overexpression. (rupress.org)
- ROCK I and II have been assumed to perform the same functions, but most studies have been accompanied by the overexpression of kinase dead, constitutively active mutant or wild-type forms of one isoform. (rupress.org)
- In conclusion, since CLP induced active fragmentation of rock 1 and rho-kinase inhibitor prevented peroxynitrite-mediated apoptotic lung injury in this CLP-induced sepsis model, this suggests that rho-kinase plays an important role in apoptotic lung injury. (biomedcentral.com)
- Rho-associated protein kinase (ROCK) was recently described as a novel neuroprotective target in PD. (readbyqxmd.com)
- SB 772077B dihydrochloride is a potent Rho-kinase (ROCK) inhibitor with a IC50 value of approximately 5.6 nM at recombinant human ROCK1 and 2. (emmx.com)
- The substrates of Rho-kinase also have been identified, including the myosin-binding subunit (MBS) of myosin phosphatase (MLCPh), ERM (ezrin, radixin, moesin) family, adducin, intermediate filament (vimentin), Na + -H + exchanger, and LIM-kinase 1 ( Figure 1 ). (ahajournals.org)
- Increased Rho-kinase activity was localized to podocytes in APN mice by immunostainings against the phosphorylated forms of Rho-kinase substrates. (uzh.ch)
Effector Rho kinase1
- Here, we identify adipocyte signaling through the guanosine triphosphatase Rho and its effector Rho-kinase as one such mechanism. (sciencemag.org)
- Results- The Rho-kinase inhibitor Y-27632 was selectively ≈3-fold more potent as a cerebral vasodilator in males versus females. (ahajournals.org)
- This entailed comparing the effects of collagenase A and trypsin in the presence and absence of a Rho kinase inhibitor, Y-27632, on proliferation and tight junctional and cytoskeletal integrity during their expansion. (molvis.org)
- This study aimed to isolate normal tonsillar keratinocytes (NTK) from human tonsils, increase the lifespan of these cells using the Rho kinase inhibitor Y-27632 and to develop tissue-engineered equivalents of healthy and infected tonsil epithelium. (whiterose.ac.uk)
- An increase in the cytoplasmic concentration of Ca 2+ leads to Ca 2+ -calmodulin complex formation which activates MLC kinase (MLCK). (bmj.com)
- A second effector is phosphoinositide 3-OH kinase (PI 3-kinase), which, in turn, activates the small G protein Rac. (asm.org)
- Ras V12S35 binds and activates Raf, Ras V12G37 binds and activates Ral GDS and Rin 1, and Ras V12C40 binds and activates PI 3-kinase ( 21 , 46 , 56 , 57 ). (asm.org)
- The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase. (pubmedcentralcanada.ca)
- To evaluate the causal relationship between Rho/Rho kinase overactivity and mechanisms of vascular dysfunction in patients with atherosclerosis. (clinicaltrials.gov)
- Qian Zhou and James K. Liao, " Rho Kinase: An Important Mediator of Atherosclerosis and Vascular Disease", Current Pharmaceutical Design (2009) 15: 3108. (eurekaselect.com)
- Rho kinase over-activation is associated with nitric oxide (NO) reduction and atherosclerosis. (biomedcentral.com)
- Inflammatory stimuli upregulate Rho-kinase in human coronary vascular smooth muscle cells," Journal of Molecular and Cellular Cardiology , vol. 37, no. 2, pp. 537-546, 2004. (hindawi.com)
- 1,2 Rho is known to modulate Ca 2+ -sensitization of vascular smooth muscle cells (VSMCs) and is thought to act by inhibiting myosin phosphatase activity. (ahajournals.org)
- Conclusions- These data indicate that vascular Rho-kinase function is suppressed in females because of the effects of estrogen, whereas the higher NO activity in females is estrogen independent. (ahajournals.org)
- 5 Evidence is accumulating to suggest that diseases such as hypertension and coronary and cerebral vasospasm are associated with increased vascular Rho-kinase activity, 5 but no study has tested whether Rho-kinase function or expression might be influenced by gender. (ahajournals.org)
- 6 Furthermore, Rho-kinase-mediated vascular tone of the basilar artery is augmented by chronic NO synthase (NOS) inhibition, 7 consistent with a normal modulatory effect of NO on Rho-kinase function. (ahajournals.org)
- In addition to increased vascular resistance, chronic hypoxia induced Rho kinase-dependent capillary angiogenesis. (ahajournals.org)
- Rho, Rac, and Cdc42 have been the most extensively characterized family members and were originally implicated in the signal transduction pathways that control actomyosin assembly in stress fibers, lamellipodia, and filopodia, respectively. (jneurosci.org)
- Furthermore, these cells have elevated levels of ERK1/2 MAP kinases, suggesting that R-Ras can activate in parts similar to signal transduction pathways of Ras (7) . (aacrjournals.org)
- Microinjection of the catalytic domain of Rho-kinase into serum-starved Swiss 3T3 cells induced the formation of stress fibers and focal adhesions, whereas microinjection of the inactive catalytic domain, the Rho-binding domain, or the pleckstrin-homology domain inhibited the LPA-induced formation of stress fibers and focal adhesions. (sciencemag.org)
- Thus, Rho-kinase appears to mediate signals from Rho and to induce the formation of stress fibers and focal adhesions. (sciencemag.org)
- Rho participates in signaling pathways that lead to the formation of actin stress fibers and focal adhesions ( 2 ). (sciencemag.org)
- The microinjection of C3 or dominant negative Rho-kinase disrupted stress fibers and weakened the accumulation of phosphorylated MBS in REF52 cells. (nih.gov)
- Rho induces stress fibers and focal adhesions ( 44 ), Rac induces accumulation of actin-rich ruffles or lamellipodia at the periphery of cells ( 45 ), and Cdc42 induces microspikes or filopodia ( 37 ). (asm.org)
- These results suggest that Rho-kinase is essential not only for actomyosin regulation but also for segregation of glial filaments into daughter cells which in turn ensures correct cytokinetic processes. (rupress.org)
- Mapping of the kinase-interacting regions of the carboxy-terminus combined with structural modeling provides insight into how these mutations likely affect the regulation of ROCK1. (gla.ac.uk)
- Pitavastatin Exhibits Protective Effects on Podocytes Accompanied by BMP-7 Up-Regulation and Rho Suppression. (semanticscholar.org)
- Horii Y, Beeler JF, Sakaguchi K, Tachibana M, Miki T. A novel oncogene, ost, encodes a guanine nucleotide exchange factor that potentially links Rho and Rac signaling pathways. (pubmedcentralcanada.ca)
Members of the Rho family1
- 1,2 At least 10 members of the Rho family are present in mammals, including Rho (isoforms A to E, and G), Rac (isoforms 1 to 3), Cdc42, and TC10. (ahajournals.org)
- At molecular level, Rho-kinase upregulates various molecules that accelerate inflammation/oxidative stress, thrombus formation, and fibrosis, whereas it downregulates endothelial nitric oxide synthase. (ahajournals.org)
- Higashi M, Hiroki J, Hattori T, Mukai Y, Morikawa K, Ichiki T, Takahashi S, Takeshita A, Shimokawa H. Long-term inhibition of Rho-kinase suppresses angiotensin II-induced cardiovascular hypertrophy in rats in vivo: effect on endothelial NAD(P)H oxidase system. (ahajournals.org)
- Activation of AMP kinase and inhibition of Rho kinase induce the mineralization of osteoblastic MC3T3-E1 cells through endothelial NOS and BMP-2 expression. (semanticscholar.org)
Specific Rho-kinase inhibitor1
- C57/BL6 mice received antipodocyte serum with or without daily treatment with the specific Rho-kinase inhibitor HA-1077 (5 mg/kg). (uzh.ch)
- Serine-threonine kinases such as protein kinase C (PKC) and Raf are usually composed of regulatory and catalytic domains ( 16 ). (sciencemag.org)
Forms of Rho-kinase1
- To elucidate the functions of Rho-kinase among these targets of Rho, we produced dominant active and negative forms of Rho-kinase. (sciencemag.org)
- n = 12 each), and were abolished by hydroxyfasudil (90 and 300 μg/kg intracoronary administration), a selective Rho-kinase inhibitor. (onlinejacc.org)
- Consistent with the frequency of ROCK1 mutations in human cancer, these results support the conclusion that there is selective pressure for the ROCK1 gene to acquire 'driver' mutations that result in kinase activation. (gla.ac.uk)
- Y-27632 dihydrochloride is a selective inhibitor of the Rho-associated protein kinase p160ROCK. (emmx.com)
- We therefore assessed the relative roles of rho-kinase and PKC in mediating vasoconstriction in arteries from three segments of the aortic and mesenteric vasculature. (aspetjournals.org)
- In the present study, we examined the roles of Rho-kinase in cytokinesis, in particular organization of glial filaments during cytokinesis. (rupress.org)
Isoform of Rho-kinase1
- 5 Rho-kinase β 3 /ROKβ 4 /ROCK1 5 is an isoform of Rho-kinase. (ahajournals.org)
Shown that Rho-kinase1
- Recent studies have shown that Rho-kinase inhibitor significantly attenuated the tubulointerstitial fibrosis in kidney induced by unilateral ureteral obstruction. (nii.ac.jp)
Activation of Rho-kinase1
- Immunoblot analysis demonstrated activation of Rho-kinase in glomeruli of antipodocyte serum-treated mice, which was prevented by HA-1077. (uzh.ch)
Involvement of Rho-kinase1
- Masumoto A, Hirooka Y, Shimokawa H, Hironaga K, Setoguchi S, Takeshita A. Possible involvement of Rho-kinase in the pathogenesis of hypertension in humans. (ahajournals.org)
Inhibition of Rho kinases2
- At cellular level, Rho-kinase mediates VSMC hypercontraction, stimulates VSMC proliferation and migration, and enhances inflammatory cell motility. (ahajournals.org)
- Fluoreseenee mireoscopy after rhodamine-phalloidin labelling of actin was used to calculate the number of actin ring structures caused by propofol or GABA, in same experiments combined with pre-incubation with C 3 exotoxin, HA- 1077 or the tyrosine kinase inhibitor Herbimycin A. Propofol-stimulated cells were studied with confocal microscopy. (diva-portal.org)
- Furthermore, w hen a tyrosine kinase bioeker was used no ring structures were formed. (diva-portal.org)
- Treatment of neurulating embryos with Y27632, a specific inhibitor of Rho kinases, blocked migration and fusion of the bilateral heart primordia, formation of the brain and neural tube, caudalward movement of Hensen's node, and establishment of normal left-right asymmetry. (biologists.org)
- In addition, specific antisense oligonucleotides significantly diminished Rho kinase mRNA levels and replicated many of the teratologies induced by Y27632. (biologists.org)
- These responses were corrected by incubation of IPAs with tiron (ROS scavenger), bardoxolone (Nrf2 activator), ML171 (NOX1 inhibitor) and Y27632 (Rho Kinase inhibitor). (ahajournals.org)
- We investigated whether Rho-kinase activation is one of the molecular mechanisms involved in defective eNOS signaling in secondary biliary cirrhosis. (wiley.com)
- Rho-kinase has been suggested as a potential therapeutic target in the treatment of cardiovascular diseases. (mdpi.com)
- Testing Rho-kinase activity in vitro, Rockout inhibits with an IC50 of 25 microM ( approximately 5-fold less potent than Y-27632) but has a similar specificity profile. (nih.gov)
- 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside inhibits proinflammatory response in glial cells: a possible role of AMP-activated protein kinase. (semanticscholar.org)
- Here we showed that hepatic Rho-kinase 1 (ROCK1) drives obesity-induced steatosis in mice through stimulation of de novo lipogenesis. (jci.org)
- Using macrophages from sphingosine kinase 2 KO (SK2KO) mice to mimic ceramide-rich conditions of atherosclerotic lesions, we show that SK2KO macrophages display impaired actin polymerization and foam cell formation in response to contact with agLDL. (harvard.edu)
- The murine Mst1 and Mst2 kinases are most abundant in tissues of the lymphoid system, and mice lacking Mst1 exhibit a variety of T cell abnormalities. (rupress.org)
- Mice fed a high-fat diet (HFD) showed increased Rho-kinase activity in adipose tissue compared to mice fed a low-fat diet. (sciencemag.org)
- Downregulation of Rho associated coiled-coil forming protein kinase 1 in the process of delayed myocardialization of cardiac proximal outflow tract septum in connexin 43 knockout mice embryo. (biomedsearch.com)
- Periodic acid staining demonstrated less podocyte hypertrophy in Rho-kinase-inhibited APN mice, despite similar amounts of immune complex deposition. (uzh.ch)
- Functionally, Rho-kinase inhibition significantly reduced proteinuria without influencing blood pressure. (uzh.ch)
- Expression of the dominant-negative form of Rho-kinase inhibited the cytokinesis of Xenopus embryo and mammalian cells, the result being production of multinuclei. (rupress.org)
- When cells are stimulated with certain extracellular signals such as LPA, GDP·Rho is believed to be converted to GTP·Rho, which binds to specific targets that mediate its biological functions. (sciencemag.org)
- Our results also suggest that the mechanism of the renoprotective effect of Rho-kinase inhibitor is partly mediated via inhibition of extracellular matrix gene expression, monocytes/macrophages infiltration, oxidative stress, and upregulation of eNOS gene expression. (nii.ac.jp)
- extracellular signal-activated kinase (ERK) cascade. (asm.org)