Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.Cyclin-Dependent Kinase 2: A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.Cyclin D1: Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.Cyclin A: A cyclin subtype that has specificity for CDC2 PROTEIN KINASE and CYCLIN-DEPENDENT KINASE 2. It plays a role in progression of the CELL CYCLE through G1/S and G2/M phase transitions.Cyclin E: A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.Cyclins: A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.Cyclin-Dependent Kinase 4: Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. It partners with CYCLIN D to phosphorylate RETINOBLASTOMA PROTEIN. CDK4 activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P16.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.CDC2-CDC28 Kinases: A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.Cell Cycle: 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.Cyclin-Dependent Kinase Inhibitor p21: A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.Cyclin-Dependent Kinase 5: A serine-threonine kinase that plays important roles in CELL DIFFERENTIATION; CELL MIGRATION; and CELL DEATH of NERVE CELLS. It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation.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.Cyclin B: A cyclin subtype that is transported into the CELL NUCLEUS at the end of the G2 PHASE. It stimulates the G2/M phase transition by activating CDC2 PROTEIN KINASE.Cyclin C: A cyclin subtype that binds to the CYCLIN-DEPENDENT KINASE 3 and CYCLIN-DEPENDENT KINASE 8. Cyclin C plays a dual role as a transcriptional regulator and a G1 phase CELL CYCLE regulator.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.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.Cyclin D: A cyclin subtype that is specific for CYCLIN-DEPENDENT KINASE 4 and CYCLIN-DEPENDENT KINASE 6. Unlike most cyclins, cyclin D expression is not cyclical, but rather it is expressed in response to proliferative signals. Cyclin D may therefore play a role in cellular responses to mitogenic signals.G1 Phase: The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors.Cyclin-Dependent Kinase Inhibitor p16: A product of the p16 tumor suppressor gene (GENES, P16). It is also called INK4 or INK4A because it is the prototype member of the INK4 CYCLIN-DEPENDENT KINASE INHIBITORS. This protein is produced from the alpha mRNA transcript of the p16 gene. The other gene product, produced from the alternatively spliced beta transcript, is TUMOR SUPPRESSOR PROTEIN P14ARF. Both p16 gene products have tumor suppressor functions.Cyclin-Dependent Kinase Inhibitor Proteins: A group of cell cycle proteins that negatively regulate the activity of CYCLIN/CYCLIN-DEPENDENT KINASE complexes. They inhibit CELL CYCLE progression and help control CELL PROLIFERATION following GENOTOXIC STRESS as well as during CELL DIFFERENTIATION.Cyclin D3: A broadly expressed type D cyclin. Experiments using KNOCKOUT MICE suggest a role for cyclin D3 in LYMPHOCYTE development.Cyclin B1: A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.Retinoblastoma Protein: Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Cyclin-Dependent Kinase 6: Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE. It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18.Cyclin-Dependent Kinase Inhibitor p57: A potent inhibitor of CYCLIN-DEPENDENT KINASES in G1 PHASE and S PHASE. In humans, aberrant expression of p57 is associated with various NEOPLASMS as well as with BECKWITH-WIEDEMANN SYNDROME.Tumor Suppressor Proteins: Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.S Phase: Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.Cyclin D2: A cyclin D subtype which is regulated by GATA4 TRANSCRIPTION FACTOR. Experiments using KNOCKOUT MICE suggest a role for cyclin D2 in granulosa cell proliferation and gonadal development.Cyclin A1: A cyclin A subtype primarily found in male GERM CELLS. It may play a role in the passage of SPERMATOCYTES into meiosis I.Microtubule-Associated Proteins: High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Apoptosis: 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.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.E2F1 Transcription Factor: An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A and activates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F1 is involved in DNA REPAIR and APOPTOSIS.Cyclin A2: A widely-expressed cyclin A subtype that functions during the G1/S and G2/M transitions of the CELL CYCLE.Phosphatidylinositol 3-Kinases: 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.Cyclin G: A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 5; cyclin G associated kinase, and PROTEIN PHOSPHATASE 2.Cell Line, Tumor: A cell line derived from cultured tumor cells.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Tumor Suppressor Protein p53: Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.Mitosis: A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.Cyclin G1: A cyclin G subtype that is constitutively expressed throughout the cell cycle. Cyclin G1 is considered a major transcriptional target of TUMOR SUPPRESSOR PROTEIN P53 and is highly induced in response to DNA damage.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.Transcription Factor DP1: A transcription factor that possesses DNA-binding and E2F-binding domains but lacks a transcriptional activation domain. It is a binding partner for E2F TRANSCRIPTION FACTORS and enhances the DNA binding and transactivation function of the DP-E2F complex.Signal Transduction: 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.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.G2 Phase: The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.E2F Transcription Factors: A family of basic helix-loop-helix transcription factors that control expression of a variety of GENES involved in CELL CYCLE regulation. E2F transcription factors typically form heterodimeric complexes with TRANSCRIPTION FACTOR DP1 or transcription factor DP2, and they have N-terminal DNA binding and dimerization domains. E2F transcription factors can act as mediators of transcriptional repression or transcriptional activation.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.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)Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Proliferating Cell Nuclear Antigen: Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.RNA, Messenger: 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.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.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.src-Family Kinases: 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.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.DNA Damage: Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.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 enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.Cyclin B2: A cyclin B subtype that colocalizes with GOLGI APPARATUS during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.Mitogen-Activated Protein Kinase 1: A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Cyclin T: A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 9. Unlike traditional cyclins, which regulate the CELL CYCLE, type T cyclins appear to regulate transcription and are components of positive transcriptional elongation factor B.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.p21-Activated Kinases: A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.Mitogen-Activated Protein Kinase 3: A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.JNK Mitogen-Activated Protein Kinases: A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Cyclin H: A cyclin subtype that is found as a component of a heterotrimeric complex containing cyclin-dependent kinase 7 and CDK-activating kinase assembly factor. The complex plays a role in cellular proliferation by phosphorylating several CYCLIN DEPENDENT KINASES at specific regulatory threonine sites.Cyclin G2: An unusual cyclin subtype that is found highly expressed in terminally differentiated cells. Unlike conventional cyclins increased expression of cyclin G2 is believed to cause a withdrawal of cells from the CELL CYCLE.Kinetics: The rate dynamics in chemical or physical systems.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.MAP Kinase Kinase Kinases: Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.3T3 Cells: 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.Creatine Kinase: 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.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Calcium: 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.Casein Kinase II: A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.eIF-2 Kinase: 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.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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Cell Nucleus: 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)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.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).MAP Kinase Kinase 1: An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.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.Casein Kinases: 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.Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.Pyruvate Kinase: ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.Glycogen Synthase Kinase 3: A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.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.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.Mice, Knockout: 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.Thymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21.MAP Kinase Kinase 4: A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.Flavonoids: A group of phenyl benzopyrans named for having structures like FLAVONES.Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Phosphotransferases (Alcohol Group Acceptor): A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.I-kappa B Kinase: A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.Mice, Inbred C57BLProto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.E2F4 Transcription Factor: An E2F transcription factor that represses GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F4 recruits chromatin remodeling factors indirectly to target gene PROMOTER REGIONS through RETINOBLASTOMA LIKE PROTEIN P130 and RETINOBLASTOMA LIKE PROTEIN P107.Recombinant Proteins: Proteins prepared by recombinant DNA technology.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.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.1-Phosphatidylinositol 4-Kinase: An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.Aurora Kinases: 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.rho-Associated 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.Protein Kinase C-alpha: A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.DNA Replication: The process by which a DNA molecule is duplicated.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.S Phase Cell Cycle Checkpoints: Cell regulatory signaling system that controls progression through S PHASE and stabilizes the replication forks during conditions that could affect the fidelity of DNA REPLICATION, such as DNA DAMAGE or depletion of nucleotide pools.Protein Kinase C-delta: A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.PhosphoproteinsRats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Proteins: 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.Oncogene Proteins: Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).Transcriptional Activation: Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.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.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Cyclin I: A cyclin subtype that is found abundantly in post-mitotic tissues. In contrast to the classical cyclins, its level does not fluctuate during the cell cycle.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Diacylglycerol Kinase: An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.Precipitin Tests: Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.Retinoblastoma-Binding Protein 1: A ubiquitously expressed regulatory protein that contains a retinoblastoma protein binding domain and an AT-rich interactive domain. The protein may play a role in recruiting HISTONE DEACETYLASES to the site of RETINOBLASTOMA PROTEIN-containing transcriptional repressor complexes.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.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.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.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Myosin-Light-Chain Kinase: 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.Focal Adhesion Protein-Tyrosine Kinases: A family of non-receptor, PROLINE-rich protein-tyrosine kinases.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.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.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.ChromonesProtein 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.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.MAP Kinase Kinase 2: A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.Androstadienes: Derivatives of the steroid androstane having two double bonds at any site in any of the rings.MAP Kinase Kinase Kinase 1: A 195-kDa MAP kinase kinase kinase with broad specificity for MAP KINASE KINASES. It is found localized in the CYTOSKELETON and can activate a variety of MAP kinase-dependent pathways.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Genes, bcl-1: The B-cell leukemia/lymphoma-1 genes, associated with various neoplasms when overexpressed. Overexpression results from the t(11;14) translocation, which is characteristic of mantle zone-derived B-cell lymphomas. The human c-bcl-1 gene is located at 11q13 on the long arm of chromosome 11.Breast Neoplasms: Tumors or cancer of the human BREAST.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.MorpholinesGene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Cyclic GMP-Dependent Protein Kinases: A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.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 enzymesPhosphoprotein Phosphatases: A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Genes, p16: Tumor suppressor genes located on human chromosome 9 in the region 9p21. This gene is either deleted or mutated in a wide range of malignancies. (From Segen, Current Med Talk, 1995) Two alternatively spliced gene products are encoded by p16: CYCLIN-DEPENDENT KINASE INHIBITOR P16 and TUMOR SUPPRESSOR PROTEIN P14ARF.Mitogen-Activated Protein Kinase 8: A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Phosphoglycerate Kinase: An enzyme catalyzing the transfer of a phosphate group from 3-phospho-D-glycerate in the presence of ATP to yield 3-phospho-D-glyceroyl phosphate and ADP. EC 2.7.2.3.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.NF-kappa B: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.MAP Kinase Kinase 6: A mitogen-activated protein kinase kinase with specificity for P38 MITOGEN-ACTIVATED PROTEIN KINASES.

Neuronal differentiation and patterning in Xenopus: the role of cdk5 and a novel activator xp35.2. (1/634)

Cdk5, a member of the cyclin-dependent kinase family, has been shown to play an important role in development of the central nervous system in mammals when partnered by its activator p35. Here we describe the cloning and characterization of a novel activator of cdk5 in Xenopus, Xp35.2. Xp35.2 is expressed during development initially in the earliest differentiating primary neurons in the neural plate and then later in differentiating neural tissue of the brain. This is in contrast to the previously described Xenopus cdk5 activator Xp35.1 which is expressed over the entire expanse of the neural plate in both proliferating and differentiating cells. Expression of both Xp35.1 and Xp35.2 and activation of cdk5 kinase occur when terminal neural differentiation is induced by neurogenin and neuro D overexpression but not when only early stages of neural differentiation are induced by noggin. Moreover, blocking cdk5 kinase activity specifically results in disruption and reduction of the embryonic eye where cdk5 and its Xp35 activators are expressed. Thus, cdk5/p35 complexes function in aspects of neural differentiation and patterning in the early embryo and particularly in formation of the eye.  (+info)

Identification and structure characterization of a Cdk inhibitory peptide derived from neuronal-specific Cdk5 activator. (2/634)

The activation of cyclin-dependent kinase 5 (Cdk5) depends on the binding of its neuronal specific activator Nck5a. The minimal activation domain of Nck5a is located in the region of amino acid residues 150 to 291 (Tang, D., Chun, A. C. S., Zhang, M., and Wang, J. H. (1997) J. Biol. Chem. 272, 12318-12327). In this work we show that a 29-residue peptide, denoted as the alphaN peptide, encompassing amino acid residues Gln145 to Asp173 of Nck5a is capable of binding Cdk5 to result in kinase inhibition. This peptide also inhibits an active phospho-Cdk2-cyclin A complex, with a similar potency. Direct competition experiments have shown that this inhibitory peptide does not compete with Nck5a or cyclin A for Cdk5 or Cdk2, respectively. Steady state kinetic analysis has indicated that the alphaN peptide acts as a non-competitive inhibitor of Cdk5. Nck5a complex with respect to the peptide substrate. To understand the molecular basis of kinase inhibition by the peptide, we determined the structure of the peptide in solution by circular dichroism and two-dimensional 1H NMR spectroscopy. The peptide adopts an amphipathic alpha-helical structure from residues Ser149 to Arg162 which can be further stabilized by the helix-stabilizing solvent trifluoroethanol. The hydrophobic face of the helix is likely to be the kinase binding surface.  (+info)

Identification of substrate binding site of cyclin-dependent kinase 5. (3/634)

Cyclin-dependent kinase 5 (CDK5), unlike other CDKs, is active only in neuronal cells where its neuron-specific activator p35 is present. However, it phosphorylates serines/threonines in S/TPXK/R-type motifs like other CDKs. The tail portion of neurofilament-H contains more than 50 KSP repeats, and CDK5 has been shown to phosphorylate S/T specifically only in KS/TPXK motifs, indicating highly specific interactions in substrate recognition. CDKs have been shown to have a high preference for a basic residue (lysine or arginine) as the n+3 residue, n being the location in the primary sequence of a phosphoacceptor serine or threonine. Because of the lack of a crystal structure of a CDK-substrate complex, the structural basis for this specific interaction is unknown. We have used site-directed mutagenesis ("charged to alanine") and molecular modeling techniques to probe the recognition interactions for substrate peptide (PKTPKKAKKL) derived from histone H1 docked in the active site of CDK5. The experimental data and computer simulations suggest that Asp86 and Asp91 are key residues that interact with the lysines at positions n+2 and/or n+3 of the substrates.  (+info)

DNA binding protein dbpA binds Cdk5 and inhibits its activity. (4/634)

Progress in the cell cycle is governed by the activity of cyclin dependent kinases (Cdks). Unlike other Cdks, the Cdk5 catalytic subunit is found mostly in differentiated neurons. Interestingly, the only known protein that activates Cdk5 (i.e. p35) is expressed solely in the brain. It has been suggested that, besides its requirement in neuronal differentiation, Cdk5 activity is induced during myogenesis. However, it is not clear how this activity is regulated in the pathway that leads proliferative cells to differentiation. In order to find if there exists any Cdk5-interacting protein, the yeast two-hybrid system was used to screen a HeLa cDNA library. We have determined that a C-terminal 172 amino acid domain of the DNA binding protein, dbpA, binds to Cdk5. Biochemical analyses reveal that this fragment (dbpA(Cdelta)) strongly inhibits p35-activated Cdk5 kinase. The protein also interacts with Cdk4 and inhibits the Cdk4/cyclin D1 enzyme. Surprisingly, dbpA(Cdelta) does not bind Cdk2 in the two-hybrid assay nor does it inhibit Cdk2 activated by cyclin A. It could be that dbpA's ability to inhibit Cdk5 and Cdk4 reflects an apparent cross-talk between distinct signal transduction pathways controlled by dbpA on the one hand and Cdk5 or Cdk4 on the other.  (+info)

Migration defects of cdk5(-/-) neurons in the developing cerebellum is cell autonomous. (5/634)

Cyclin-dependent kinase 5 (Cdk5) is a member of the family of cell cycle-related kinases. Previous neuropathological analysis of cdk5(-/-) mice showed significant changes in CNS development in regions from cerebral cortex to brainstem. Among the defects in these animals, a disruption of the normal pattern of cell migrations in cerebellum was particularly apparent, including a pronounced abnormality in the location of cerebellar Purkinje cells. Complete analysis of this brain region is hampered in the mutant because most of cerebellar morphogenesis occurs after birth and the cdk5(-/-) mice die in the perinatal period. To overcome this disadvantage, we have generated chimeric mice by injection of cdk5(-/-) embryonic stem cells into host blastocysts. Analysis of the cerebellum from the resulting cdk5(-/-) left arrow over right arrow cdk5(+/+) chimeric mice shows that the abnormal location of the mutant Purkinje cells is a cell-autonomous defect. In addition, significant numbers of granule cells remain located in the molecular layer, suggesting a failure to complete migration from the external to the internal granule cell layer. In contrast to the Purkinje and granule cell populations, all three of the deep cerebellar nuclear cell groupings form correctly and are composed of cells of both mutant and wild-type genotypes. Despite similarities of the cdk5(-/-) phenotype to that reported in reeler and mdab-1(-/-) (scrambler/yotari) mutant brains, reelin and disabled-1 mRNA were found to be normal in cdk5(-/-) brain. Together, the data further support the hypothesis that Cdk5 activity is required for specific components of neuronal migration that are differentially required by different neuronal cell types and by even a single neuronal cell type at different developmental stages.  (+info)

Regulation of cyclin-dependent kinase 5 catalytic activity by phosphorylation. (6/634)

Cyclin-dependent kinase 5 (cdk5) is found in an active form only in neuronal cells. Activation by virtue of association with the cyclin-like neuronal proteins p35 (or its truncated form p25) and p39 is the only mechanism currently shown to regulate cdk5 catalytic activity. In addition to cyclin binding, other members of the cdk family require for maximal activation phosphorylation of a Ser/Thr residue (Thr(160) in the case of cdk-2) that is conserved in all cdks except cdk8. This site is phosphorylated by cdk-activating kinases, which, however, do not phosphorylate cdk5. To examine the possible existence of a phosphorylation-dependent regulatory mechanism in the case of cdk5, we have metabolically labeled PC12 cells with (32)P(i) and shown that the endogenous cdk5 is phosphorylated. Bacterially expressed cdk5 also can be phosphorylated by PC12 cell lysates. Phosphorylation of cdk5 by a PC12 cell lysate results in a significant increase in cdk5/p25 catalytic activity. Ser(159) in cdk5 is homologous to the regulatory Thr(160) in cdk2. A Ser(159)-to-Ala (S159A) cdk5 mutant did not show similar activation, which suggests that cdk5 is also regulated by phosphorylation at this site. Like other members of the cdk family, cdk5 catalytic activity is influenced by both p25 binding and phosphorylation. We show that the cdk5-activating kinase (cdk5AK) is distinct from the cdk-activating kinase (cyclin H/cdk7) that was reported previously to neither phosphorylate cdk5 nor affect its activity. We also show that casein kinase I, but not casein kinase II, can phosphorylate and activate cdk5 in vitro.  (+info)

Inhibition of tau phosphorylating protein kinase cdk5 prevents beta-amyloid-induced neuronal death. (7/634)

The key target of this study was the tau protein kinase II system (TPK II) involving the catalytic subunit cdk5 and the regulatory component p35. TPK II is one of the tau phosphorylating systems in neuronal cells, thus regulating its functions in the cytoskeletal dynamics and the extension of neuronal processes. This research led to demonstration that the treatment of rat hippocampal cells in culture with fibrillary beta-amyloid (Abeta) results in a significant increase of the cdk5 enzymatic activity. Interestingly, the data also showed that the neurotoxic effect of 1-20 microM Abeta on primary cultures markedly diminished with co-incubation of hippocampal cells with the amyloid fibers plus the cdk5 inhibitor butyrolactone I. This inhibitor protected brain cells against Abeta-induced cell death in a concentration dependent fashion. Moreover, death was also prevented by a cdk5 antisense probe, but not by an oligonucleotide with a random sequence. The cdk5 antisense also reduced neuronal expression of cdk5 compared with the random oligonucleotide. The studies indicate that cdk5 plays a major role in the molecular path leading to the neurodegenerative process triggered by the amyloid fibers in primary cultures of rat hippocampal neurons. These findings are of interest in the context of the pathogenesis of Alzheimer's disease.  (+info)

Neuron-specific Cdk5 kinase is responsible for mitosis-independent phosphorylation of c-Src at Ser75 in human Y79 retinoblastoma cells. (8/634)

c-Src is phosphorylated at specific serine and threonine residues during mitosis in fibroblastic and epithelial cells. These sites are phosphorylated in vitro by the mitotic kinase Cdk1 (p34(cdc2)). In contrast, c-Src in Y79 human retinoblastoma cells, which are of neuronal origin, is phosphorylated at one of the mitotic sites, Ser75, throughout the cell cycle. The identity of the serine kinase that nonmitotically phosphorylates c-Src on Ser75 remains unknown. We now are able to show for the first time that Cdk5 kinase, which has the same consensus sequence as the Cdk1 and Cdk2 kinases, is required for the phosphorylation in asynchronous Y79 cells. The Ser75 phosphorylation was inhibited in a dose-dependent manner by butyrolactone I, a specific inhibitor of Cdk5-type kinases. Three stable subclones that have almost no kinase activity were selected by transfection of an antisense Cdk5-specific activator p35 construct into Y79 cells. The loss of the kinase activity caused an approximately 85% inhibition of the Ser75 phosphorylation. These results present compelling evidence that Cdk5/p35 kinase is responsible for the novel phosphorylation of c-Src at Ser75 in neuronal cells, raising the intriguing possibility that c-Src acts as an effector of Cdk5/p35 kinase during neuronal development.  (+info)

*Cyclin-dependent kinase 5

... membrane-associated neuronal kinase, cyclin-dependent kinase 5/p35-regulated kinase". The Journal of Neuroscience. 23 (12): ... Unlike other cyclin dependent kinases, CDK5 does not also require phosphorylation on the T loop so that binding with the ... Cyclin-Dependent Kinase 5 at the US National Library of Medicine Medical Subject Headings (MeSH) CDK5 human gene location in ... The protein encoded by this gene is part of the cyclin-dependent kinase family. Recently Cdk5 has emerged as an essential ...

*Reelin

Cyclin-dependent kinase 5 (Cdk5), a major regulator of neuronal migration and positioning, is known to phosphorylate DAB1 and ... Beffert U, Weeber EJ, Morfini G, Ko J, Brady ST, Tsai LH, Sweatt JD, Herz J (Feb 2004). "Reelin and cyclin-dependent kinase 5- ... Ohshima T, Suzuki H, Morimura T, Ogawa M, Mikoshiba K (Apr 2007). "Modulation of Reelin signaling by Cyclin-dependent kinase 5 ... Keshvara L, Magdaleno S, Benhayon D, Curran T (Jun 2002). "Cyclin-dependent kinase 5 phosphorylates disabled 1 independently of ...

*CDK5R1

Cyclin-dependent kinase 5 activator 1 is an enzyme that in humans is encoded by the CDK5R1 gene. The protein encoded by this ... "Entrez Gene: CDK5R1 cyclin-dependent kinase 5, regulatory subunit 1 (p35)". Hoek KS, Schlegel NC, Eichhoff OM, et al. (2008). " ... Floyd SR, Porro EB, Slepnev VI, Ochoa GC, Tsai LH, De Camilli P (March 2001). "Amphiphysin 1 binds the cyclin-dependent kinase ... Dhavan R, Greer PL, Morabito MA, Orlando LR, Tsai LH (September 2002). "The cyclin-dependent kinase 5 activators p35 and p39 ...

*SH3GLB1

Lee SY, Wenk MR, Kim Y, Nairn AC, De Camilli P (2004). "Regulation of synaptojanin 1 by cyclin-dependent kinase 5 at synapses ... 10 (5): 703-13. doi:10.1101/gr.10.5.703. PMC 310876 . PMID 10810093. Modregger J, Schmidt AA, Ritter B, Huttner WB, Plomann M ( ... 4 (5): 345-9. doi:10.1093/dnares/4.5.345. PMID 9455484. Howard L, Nelson KK, Maciewicz RA, Blobel CP (1999). "Interaction of ... "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1-2): 149-56. doi: ...

*Ed Harlow

"Distinct roles for cyclin-dependent kinases in cell cycle control." Science 262.5142 (1993): 2050-2054. Harlow, E. D., et al. " ... "p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5." (1994): 419-423. Meyerson, Matthew, et al. "A family ... Tsai, L (1994). "p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5". Nature. 371: 419-23. doi:10.1038/ ... van den Heuvel, S (1993). "Distinct roles for cyclin-dependent kinases in cell cycle control". Science. 262: 2050-4. doi: ...

*STXBP1

"Regulation of exocytosis by cyclin-dependent kinase 5 via phosphorylation of Munc18". J. Biol. Chem. 274 (7): 4027-35. doi: ... Putative role in insulin-dependent movement of GLUT-4". J. Biol. Chem. 272 (10): 6179-86. doi:10.1074/jbc.272.10.6179. PMID ... "Phosphorylation of Munc-18/n-Sec1/rbSec1 by protein kinase C: its implication in regulating the interaction of Munc-18/n-Sec1/ ... "Phosphorylation of Munc18 by protein kinase C regulates the kinetics of exocytosis". J. Biol. Chem. 278 (12): 10538-45. doi: ...

*Li-Huei Tsai

In the Harlow laboratory, Tsai studied cyclin-dependent kinases in order to identify their role in cell division. Tsai became ... "p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5". Nature. 371 (6496): 419-423. doi:10.1038/371419a0. ... "Activity and expression pattern of cyclin-dependent kinase 5 in the embryonic mouse nervous system". Development. 119 (4): 1029 ... "The cdk5/p35 kinase is essential for neurite outgrowth during neuronal differentiation". Genes & Development. 10 (7): 816-825. ...

*Nestin (protein)

... has been shown to interact with Cyclin-dependent kinase 5. GRCh38: Ensembl release 89: ENSG00000132688 - ... "Mitotic reorganization of the intermediate filament protein nestin involves phosphorylation by cdc2 kinase". J. Biol. Chem. 276 ... 5 (12): 3310-28. PMID 4078630. Lothian C, Lendahl U (1997). "An evolutionarily conserved region in the second intron of the ...

*Dopamine receptor

Sustained D1 receptor activity is kept in check by Cyclin-dependent kinase 5. Dopamine receptor activation of Ca2+/calmodulin- ... dependent protein kinase II can be cAMP dependent or independent. The cAMP mediated pathway results in amplification of PKA ... Beta arrestin has been shown to form complexes with MAP kinase, leading to activation of Extracellular signal-regulated kinases ... Dopamine receptors can also transactivate Receptor tyrosine kinases. Beta Arrestin recruitment is mediated by G-protein kinases ...

*Beta-secretase 2

"Neuron-specific phosphorylation of Alzheimer's beta-amyloid precursor protein by cyclin-dependent kinase 5". Journal of ... "In vitro phosphorylation of the cytoplasmic domain of the amyloid precursor protein by glycogen synthase kinase-3beta". Journal ... 16 (5): 609-19. doi:10.1006/mcne.2000.0884. PMID 11083922. Hussain I, Christie G, Schneider K, Moore S, Dingwall C (Jun 2001 ...

*NMDA receptor

"Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control of NMDAR degradation". Nat. Neurosci. 10 (7): ... Neuroscience portal Calcium/calmodulin-dependent protein kinases Laube B, Hirai H, Sturgess M, Betz H, Kuhse J (1997). " ... Reelin modulates NMDA function through Src family kinases and DAB1. significantly enhancing LTP in the hippocampus. Src kinase ... "MHC class I immune proteins are critical for hippocampus-dependent memory and gate NMDAR-dependent hippocampal long-term ...

*STX1A

"Regulation of Munc-18/syntaxin 1A interaction by cyclin-dependent kinase 5 in nerve endings". The Journal of Biological ... Syntaxins bind synaptotagmin in a calcium-dependent fashion and interact with voltage dependent calcium and potassium channels ... Li C, Ullrich B, Zhang JZ, Anderson RG, Brose N, Südhof TC (June 1995). "Ca(2+)-dependent and -independent activities of neural ... Beckman ML, Bernstein EM, Quick MW (August 1998). "Protein kinase C regulates the interaction between a GABA transporter and ...

*NDEL1

... has been shown to interact with Cyclin-dependent kinase 5, YWHAE, PAFAH1B1 and DISC1. GRCh38: Ensembl release 89: ... Phosphorylation regulates the cell cycle-dependent distribution of this protein, with a fraction of the protein bound strongly ... 44 (5): 809-21. doi:10.1016/j.neuron.2004.11.019. PMID 15572112. Hayashi MA, Portaro FC, Bastos MF, Guerreiro JR, Oliveira V, ... ATF4/5 and NUDEL: regulation and loss of interaction with mutation". Human Molecular Genetics. 12 (13): 1591-608. doi:10.1093/ ...

*CDK5R2

Cyclin-dependent kinase 5 activator 2 is an enzyme that in humans is encoded by the CDK5R2 gene. The protein encoded by this ... "Entrez Gene: CDK5R2 cyclin-dependent kinase 5, regulatory subunit 2 (p39)". Dhavan, Rani; Greer Paul L; Morabito Maria A; ... 2002). "The cyclin-dependent kinase 5 activators p35 and p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent ... 2005). "Association of cyclin-dependent kinase 5 and neuronal activators p35 and p39 complex in early-onset Alzheimer's disease ...

*Aminoacyl tRNA synthetase

Arif, A; Jai, J (Jan 25, 2011). "Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin-dependent kinase 5 dictates ... 42 (5): 1703-13. doi:10.1007/s00726-011-0872-8. PMID 21400228. Prokaryotic AARS database: Chaliotis et al., (2017). The complex ... Peter G. Schultz, Expanding the genetic code Ludmerer, SW; Schimmel, P (August 5, 1987). "Construction and analysis of ...

*TRPV1

"Cyclin-dependent kinase 5 modulates nociceptive signaling through direct phosphorylation of transient receptor potential ... Phosphorylation of TRPV1 by protein kinase C have been shown to play a role in sensitization of TRPV1. The cleavage of PIP2 by ... Certain metabolites of polyunsaturated fatty acids have been shown to stimulate cells in a TRPV1-dependent fashion. The ... Premkumar LS, Ahern GP (December 2000). "Induction of vanilloid receptor channel activity by protein kinase C". Nature. 408 ( ...

*Neurofibrillary tangle

Cyclin-dependent kinase 5 (CDK5) is a kinase that has been previously hypothesized to contribute to tau pathologies. RNA ... A protein called kinase p38γ phosphorylates tau at the threonine-205 amino acid. The activity of this gamma kinase enzyme is ... It was found that the degree of tau pathology was dependent on time and the level of gene expression. Groups receiving a ... However increasing the activity of kinases has been shown to be difficult). Traditionally believed to play a major role in ...

*Addiction-related structural neuroplasticity

"Cocaine-induced proliferation of dendritic spines in nucleus accumbens is dependent on the activity of cyclin-dependent kinase- ... 5". Neuroscience. 116: 19-22. doi:10.1016/s0306-4522(02)00560-2. Sklair-Tavron, L. (1996). "Chronic morphine induces visible ...

*CDKL5

... is a gene that provides instructions for making a protein called cyclin-dependent kinase-like 5 also known as serine/ ... "Preclinical Program for Cyclin-Dependent Kinase-Like 5 (CDKL5) Deficiency". Amicus Therapeutics Press Release. 6 July 2016. ... Cyclin-dependent kinase Rett syndrome West syndrome GRCh38: Ensembl release 89: ENSG00000008086 - Ensembl, May 2017 GRCm38: ... The CDKL5 protein acts as a kinase, which is an enzyme that changes the activity of other proteins by adding a cluster of ...

*NPEPPS

Cyclin-dependent kinase 5 SOD1 TAU Tetrahydropyridine β-amyloid GRCh38: Ensembl release 89: ENSG00000141279 - Ensembl, May 2017 ... Huber RJ, Catalano A, O'Day DH (January 2013). "Cyclin-dependent kinase 5 is a calmodulin-binding protein that associates with ... 26 (5): 1385-96. doi:10.1038/sj.emboj.7601592. PMC 1817637 . PMID 17318184. Kudo LC, Parfenova L, Ren G, Vi N, Hui M, Ma Z, Lau ... 51 (5): 549-60. doi:10.1016/j.neuron.2006.07.019. PMID 16950154. Rawson NS (November 2009). "Access to linked administrative ...

*PAK1

... has been shown to interact with: ARHGEF2, ARPC1B, BMX, C-Raf, CDC42, Cyclin-dependent kinase 5, DYNLL1, LIMK1, NCK1, ... Martin GA, Bollag G, McCormick F, Abo A (May 1995). "A novel serine kinase activated by rac1/CDC42Hs-dependent ... Shin YJ, Kim YB, Kim JH (September 2013). "Protein kinase CK2 phosphorylates and activates p21-activated kinase 1". Molecular ... hyperactive Rac3 controls proliferation of breast cancer cells by a p21-activated kinase-dependent pathway". Proceedings of the ...

*KCNB1

There are 16 phosphorylation sites that are subject to the activity of kinases, such as cyclin-dependent kinase 5 and AMP- ... "Potassium channel, voltage-dependent, beta subunit, KCNAB1 (IPR005400)". InterPro. EMBL-EBI. Retrieved 2017-04-04. Wray D (May ... However, this relationship is not static and is cell dependent. The role of phosphorylation can be affected by reactive oxygen ... ROS act to increase the levels of zinc (Zn2+) and calcium (Ca2+) intracellularly that act with protein kinases to phosphorylate ...

*Tau-protein kinase

"Characterization of tau phosphorylation in glycogen synthase kinase-3beta and cyclin dependent kinase-5 activator (p23) ... protein tau kinase, STK31, tau kinase, [tau-protein] kinase, tau-protein kinase I, tau-protein kinase II, tau-tubulin kinase, ... "A novel tubulin-dependent protein kinase forming a paired helical filament epitope on tau". J. Biochem. Tokyo. 104 (3): 319-21 ... purification and crystallization of human tau-protein kinase I/glycogen synthase kinase-3beta". Acta Crystallogr. D. 56 (Pt 11 ...

*LMTK2

... membrane-associated neuronal kinase, cyclin-dependent kinase 5/p35-regulated kinase". The Journal of Neuroscience. 23 (12): ... membrane-associated neuronal kinase, cyclin-dependent kinase 5/p35-regulated kinase". The Journal of Neuroscience. 23 (12): ... It phosphorylates other proteins, and is itself also phosphorylated when interacting with cyclin-dependent kinase 5 (cdk5)/p35 ... LMTK2 has been shown to interact with PPP1CA, Cyclin-dependent kinase 5 and PPP1R2. GRCh38: Ensembl release 89: ENSG00000164715 ...

*Conditional gene knockout

... in mouse brain thought to be involved in the onset of Alzheimer's disease which codes for the enzyme cyclin-dependent kinase 5 ... Retrieved 5 November 2015. Gondo, Y (2008). "Trends in large-scale mouse mutagenesis: from genetics to functional genomics". ...

*Cell cycle

Two key classes of regulatory molecules, cyclins and cyclin-dependent kinases (CDKs), determine a cell's progress through the ... cyclin A, DNA polymerase, thymidine kinase, etc. Cyclin E thus produced binds to CDK2, forming the cyclin E-CDK2 complex, which ... Nigg EA (June 1995). "Cyclin-dependent protein kinases: key regulators of the eukaryotic cell cycle". BioEssays. 17 (6): 471-80 ... Cyclin D is the first cyclin produced in the cell cycle, in response to extracellular signals (e.g. growth factors). Cyclin D ...
p35 is an activating co-factor of Cyclin-dependent kinase 5 (Cdk5), a protein whose dysfunction has been implicated in a wide-range of neurological disorders including cognitive impairment and disease. Inducible deletion of the p35 gene in adult mice results in profound deficits in hippocampal-dependent spatial learning and synaptic physiology, however the impact of the loss of p35 function on hippocampal in vivo physiology and spatial coding remains unknown. Here, we recorded CA1 pyramidal cell activity in freely behaving p35 cKO and control mice and found that place cells in the mutant mice have elevated firing rates and impaired spatial coding, accompanied by changes in the temporal organization of spiking both during exploration and rest. These data shed light on the role of p35 in maintaining cellular and network excitability and provide a physiological correlate of the spatial learning deficits in these mice.
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
The 85211BI-03 is a low skew, high performance 1-to-2 Differential-to-LVHSTL Fanout Buffer. The CLK, nCLK pair can accept most standard differential input levels.The 85211BI-03 is characterized to operate from a 3.3V power supply. Guaranteed output and part-to-part skew characteristics make the 85211BI-03 ideal for those clock distribution applications demanding well defined performance and repeatability. ...
Epidemiological studies indicate that populations taking anti-inflammatory drugs have a significantly reduced prevalence of AD, or a slower mental decline (McGeer et al., 1998). This paper demonstrated how inflammation due to microglial activation might affect tau pathology through Aβ. Aβ deposition activates microglia, which then enhanced an inflammatory response. The authors reported that LPS-evoked inflammation induced tau phosphorylation by activating CDK5, which in turn follows from increasing the level of CDK5 activator p25. Taken together with the epidemiological study, tau appears to play a crucial role in AD and in the rate of mental decline during the disease.. The authors also write that the accumulation of p25 by LPS treatment that they observed is similar to observations of p25 accumulation in AD brain. They showed that LPS induced the accumulation of p25, and tau phosphorylation in non-Tg mouse. However, this accumulation is still controversial. Some reports showed no difference ...
The 8T33FS6221 is designed for low skew clock distribution systems and supports clock frequencies up to 2GHz. The device accepts two clock sources. The CLK0 input can be driven by PECL compatible signals, the CLK1 input accepts HSTL compatible signals. The selected input signal is distributed to 20 identical, differential PECL outputs. If VBB is connected to the nCLK0 or nCLK1 input and bypassed to GND by a 10nF capacitor, the 8T33FS6221 can be driven by single-ended PECL signals utilizing the VBB bias voltage output ...
Combined effects of increasing numbers of the risk alleles from CDKAL1-rs9465871, CDKN2A/B-rs10811661, IGF2BP2-rs4402960, and SLC30A8-rs13266634. A: The risk al
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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.
Cyclin-dependent kinase 4 (CDK4) is a member of cyclin-dependent kinase family which regulates G1 to S cell cycle transition. CDK4 activity is increased in many tumor types. Here, we report a...
Urolithiasis impacts around 10% of the united states population with a growing price of prevalence recurrence and penetrance. at measurable amounts and several have got distinctive distribution patterns. Manipulation from the levels of a few of these elemental the different parts of calcium-based rocks has led to clinically beneficial adjustments in rock chemistry and price […]. ...
Cyclin-dependent kinases (CDKs) are core components of the cell cycle machinery that govern the transition between phases during cell cycle progression. Genes involved in cell cycle are frequently mutated in human cancer and deregulated CDK activity repr
Vol 7: PD-0332991 induces G1 arrest of colorectal carcinoma cells through inhibition of the cyclin-dependent kinase-6 and retinoblastoma protein axis.. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
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p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
View mouse Cdk11b Chr4:155624854-155649938 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
1GIH: Crystallographic approach to identification of cyclin-dependent kinase 4 (CDK4)-specific inhibitors by using CDK4 mimic CDK2 protein.
pep:known chromosome:VEGA66:5:146231288:146302874:1 gene:OTTMUSG00000025856 transcript:OTTMUST00000063710 gene_biotype:protein_coding transcript_biotype:protein_coding gene_symbol:Cdk8 description:cyclin-dependent kinase 8 ...
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Looking for online definition of cyclin-dependent kinase 15 in the Medical Dictionary? cyclin-dependent kinase 15 explanation free. What is cyclin-dependent kinase 15? Meaning of cyclin-dependent kinase 15 medical term. What does cyclin-dependent kinase 15 mean?
TY - JOUR. T1 - The PI3K-Akt-mTOR pathway regulates a oligomer induced neuronal cell cycle events. AU - Bhaskar, Kiran. AU - Miller, Megan. AU - Chludzinski, Alexandra. AU - Herrup, Karl. AU - Zagorski, Michael. AU - Lamb, Bruce T.. PY - 2009/4/13. Y1 - 2009/4/13. N2 - Accumulating evidence suggests that neurons prone to degeneration in Alzheimers Disease (AD) exhibit evidence of re-entry into an aberrant mitotic cell cycle. Our laboratory recently demonstrated that, in a genomic amyloid precursor protein (APP) mouse model of AD (R1.40), neuronal cell cycle events (CCEs) occur in the absence of beta-amyloid (A) deposition and are still dependent upon the amyloidogenic processing of the amyloid precursor protein (APP). These data suggested that soluble A species might play a direct role in the induction of neuronal CCEs. Here, we show that exposure of non-transgenic primary cortical neurons to A oligomers, but not monomers or fibrils, results in the retraction of neuronal processes, and ...
The cyclin-dependent kinase Cdk5 has diverse functions in the brain, and has been implicated in Alzheimer disease in multiple contexts. The Cdk5 activator p25 has been reported to be elevated in AD brain and causes neurodegeneration in mice (see ARF related news story). The kinase phosphorylates tau (see ARF related news story) and contributes to Aβ production (see ARF related news story) and dendritic spine loss (see ARF related news story).. Now, Karen Duff and colleagues at Columbia University in New York have identified another potentially pathologic action of Cdk5. In the March 13 Neuron, they show that the p25-mediated activation of Cdk5 can increase production of Aβ via transcriptional induction of β-secretase 1 (BACE1) gene expression. Treating p25 transgenic mice with a Cdk5 kinase inhibitor reversed the elevation of BACE and reduced amyloid production, suggesting that the kinase could be a target for an amyloid-lowering strategy.. To gauge the effect of Cdk5 activation on BACE, ...
Instantly find & access educational materials and complete eLearning activities at your leisure. Native iPad/iPhone/Android Apps are available for the convenience of on-the-go users.
P 276 is a flavone that selectively inhibits the cyclin-dependent kinases Cdk4-D1, Cdk9-T and Cdk1-B, thus inhibiting the pathways necessary for cancer cell
DRP-2, also known as collapsin response mediator protein-2 (CRMP-2), is expressed at high levels in the developing nervous system and plays a critical…
Cdk5r1 - Cdk5r1 (Myc-DDK-tagged ORF) - Rat cyclin-dependent kinase 5, regulatory subunit 1 (p35) (Cdk5r1), (10 ug) available for purchase from OriGene - Your Gene Company.
A stable environment minimizes evapora- tive heat loss. 10. Cyclin-dependent kinases participate recomendaad death of neurons evoked by DNA- damaging agents. Daleiden, A.
HHEX - HHEX - Human, 4 unique 29mer shRNA constructs in retroviral RFP vector shRNA available for purchase from OriGene - Your Gene Company.
The i-CDK9-induced increase in CDK9s binding to the MYC locus is mostly BRD4-dependent.DOI:http://dx.doi.org/10.7554/eLife.06535.017
TY - JOUR. T1 - Phosphorylation of CRMP2 (Collapsin Response Mediator Protein 2) is Involved in Proper Dendritic Field Organization. AU - Yamashita, Naoya. AU - Ohshima, Toshio. AU - Nakamura, Fumio. AU - Kolattukudy, Papachan. AU - Honnorat, Jérôme. AU - Mikoshiba, Katsuhiko. AU - Goshima, Yoshio. PY - 2012/1/25. Y1 - 2012/1/25. N2 - Collapsin response mediator proteins (CRMPs) are intracellular proteins that mediate signals for several extracellular molecules, such as Semaphorin3A and neurotrophins. The phosphorylation of CRMP1 and CRMP2 by Cdk5 at Ser522 is involved in axonal guidance and spine development. Here, we found that the Ser522-phosphorylated CRMP1 and/or CRMP2 are enriched in the dendrites of cultured cortical neurons and P7 cortical section. To determine the physiological role of CRMPs in dendritic development, we generated CRMP2 knock-in mutant mice (crmp2ki/ki) in which the Ser residue at 522 was replaced with Ala. Strikingly, the cortical basal dendrites of double mutant ...
Cyclin-Dependent Kinase 6: Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE. It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18.
Cyclin-Dependent Kinase 4: Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. It partners with CYCLIN D to phosphorylate RETINOBLASTOMA PROTEIN. CDK4 activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P16.
TY - JOUR. T1 - Alterations in cyclin-dependent protein kinase 5 (CDK5) protein levels, activity and immunocytochemistry in canine motor neuron disease. AU - Green, Sherril L.. AU - Vulliet, Philip R. AU - Pinter, Martin J.. AU - Cork, Linda C.. PY - 1998/11. Y1 - 1998/11. N2 - Hereditary canine spinal muscular atrophy (HCSMA) is a dominantly inherited motor neuron disease in Brittany spaniels that is clinically characterized by progressive muscle weakness leading to paralysis. Histopathologically, degeneration is confined to motor neurons with accumulation of phosphorylated neurofilaments in axonal internodes. Cyclin- dependent kinase 5 (CDK5), a kinase related to the cell cycle kinase cdc2, phosphorylates neurofilaments and regulates neurofilament dynamics. We examined CDK5 activity, protein levels, and cellular immunoreactivity in nervous tissue from dogs with HCSMA, from closely age-matched controls and from dogs with other neurological diseases. On immunoblot analysis, CDK5 protein levels ...
... cellular proliferation via inhibition of CDK activities. routine and g27Kip1 (hereafter g27) can regulate CDK actions.1-3 The p27 protein was originally known as an inhibitor of CDK activities for things containing CDK2 and shown to inhibit cyclin E and cyclin A activities which regulate G1 and S phase traverse.4-6 In addition to CDK inhibition, g27 provides other multifarious connections with cyclin N/cdk4 processes putatively.7 Since cellular amounts of g27 are elevated in response to high cell thickness, serum deprival, and TGF, it was hypothesized g27 brought cells into quiescence and held them in G0 through the inhibition of CDK actions.8 Numerous reviews have got characterized the control of p27 including the control of its transcription,9,10 translation,11,12 post-translational adjustments.7,13,14 cellular localization15-19 and balance.20-23 The regulations of its stability has a main role in adjusting mobile ...
The graphic displays domains and Protease cut sites on the protein sequence. Drag your mouse right/left over the graphic. Use the selection boxes on the right to select which annotations to view simultaneously. Combine annotation with multiple checkmarks.. ...
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.
EMMX proudly develops novel molecules and reagents to drug discovery and cancer research. We are scientists driven by a devotion to discovery and innovation, and we work hard every day to find new ways to streamline life science research.. ...
The worlds first wiki where authorship really matters. Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts.
The researchers examined a protein called cyclin-dependent kinase 2 (CDK2), which works as a "quality control inspector." As normal cells divide, they pause in the replication process when they find inaccurate genetic code embedded in their DNA. The health and well-being of offspring cells depends on accurate genetic code transfer from one generation of cells to the next. The Mayo researchers showed that when errors in genes are irreparable, CDK2 modifies another cellular protein -- FOXO1 -- to send a signal that results in the death of the cell. This protein-to-protein relationship invites targeted drug intervention to control unregulated growth of cancer cells ...
CDK3 antibody [N1C2] (cyclin-dependent kinase 3) for WB. Anti-CDK3 pAb (GTX105047) is tested in Human samples. 100% Ab-Assurance.
CDK8 antibody (cyclin-dependent kinase 8) for ICC/IF, IP, WB. Anti-CDK8 pAb (GTX22955) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance.
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Looking for online definition of Cyclin-dependent Kinase-like 3 in the Medical Dictionary? Cyclin-dependent Kinase-like 3 explanation free. What is Cyclin-dependent Kinase-like 3? Meaning of Cyclin-dependent Kinase-like 3 medical term. What does Cyclin-dependent Kinase-like 3 mean?
[51 Pages Report] Check for Discount on Cyclin-Dependent Kinase 1 (p34 Protein Kinase or Cell Division Protein Kinase 1 or CDK1 or EC 2.7.11.22) - Pipeline Review, H1 2016 report by Global Markets Direct. Global Markets Directs, Cyclin-Dependent Kinase 1 (p34 Protein...
Cardiac hypertrophy leading to heart failure remains a leading cause of morbidity and mortality in the 21st century despite major therapeutic advances. Improved understanding of novel molecular and cellular processes contributing to cardiac hypertrophy therefore continues to be important. Cyclin-dependent Kinase 9 (CDK9), part of a family of proteins controlling cell cycle and growth, has emerged as one such potential candidate over the last 5 years. CDK9 is the catalytic subunit of the CDK9/CyclinT complex and acts by phosphorylating the carboxy-terminal domain of RNA polymerase II. Hypertrophic signals, such as Endothelin-1 (ET-1) and phenylephrine, have been shown to cause CDK9 activation leading to a hypertrophic response in cultured mouse cardiomyocytes associated with reactivation of the foetal gene program. CDK9 also forms a complex with GATA4 to play a role in differentiation of mouse ES cells into cardiomyocytes. These findings suggest a specific role for CDK9 in controlling growth and ...
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2494 Cyclin I (CCNI) is a member of the recently described inhibitory class of cyclin proteins. The other members of this class, cyclins G1 and G2, have been implicated in the induction of cell cycle arrest. Cyclin I is widely expressed in terminally differentiated tissues, but its function remains to be determined. We previously identified cyclin I as antigenic in a mouse model of ovarian cancer. Here, we examined expression of the human cyclin I gene in normal tissues, in tumor cell lines, and in primary human ovarian tumors. By Northern blot analysis, cyclin I was expressed at moderate to high levels in all normal tissues examined, including normal ovary. In contrast, cyclin I mRNA was dramatically reduced in nine of twenty-five ovarian tumor samples examined. These studies were confirmed and extended using quantitative real-time PCR analysis. More than half of the tumors evaluated had very low levels of cyclin I mRNA compared to the expression levels in normal ovarian tissue and other normal ...
Principal Investigator:ANDO Shoji, Project Period (FY):1996 - 1997, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Bioorganic chemistry
DESCRIPTION (provided by applicant): This Phase II SBIR project is aimed at developing a novel type of drugs, termed SNX9-class compounds, with a unique combination of two anticancer activities. The first is a selective antiproliferative effect on tumor cells relative to normal cells. The second is the inhibition of chemotherapy- or radiation-induced expression of multiple genes encoding secreted tumor-supporting factors with mitogenic, antiapoptotic and angiogenic activities; as a result, SNX9-class compounds potentiate the induction of apoptosis by conventional chemotherapeutic drugs. Studies conducted during Phase I of this project showed that both activities of SNX9- class compounds are due to their ability to inhibit CDK3. This understudied member of the cyclin-dependent kinase (CDK) family is apparently unneeded by normal cells, based on its very low expression in normal human tissues and spontaneous germline inactivation in laboratory mice. However, CDK3 is overexpressed in different ...
MONARCH 1: Final overall survival analysis of a phase 2 study of abemaciclib, a CDK4 and CDK6 inhibitor, as monotherapy, in patients with HR+/HER2- breast cancer, after chemotherapy for advanced ...
Kinase selectivity studies (Fig. 1C) did not reveal major differences in selectivity between (R)-roscovitine and N-&-N1. We investigated the possibility of altered selectivity toward other targets using an indirect affinity chromatography approach on immobilized (R)-roscovitine (Fig. 2) and increasing concentrations of either free N-&-N1 or free (R)-roscovitine. This competition-based assay revealed that, compared with (R)-roscovitine, N-&-N1 appears to have a much reduced affinity for Erk2 and PDXK. This point is of importance as interaction of (R)-roscovitine with PDXK may dilute its effects in a cellular context by reducing the amount of (R)-roscovitine that is free to interact with the CDK targets. Reduced binding to PDXK, as observed with N-&-N1, is expected to lead to enhanced biological effects at lower concentrations, with most of the N-&-N1 targeting CDKs directly, rather than being diverted to PDXK.. Indeed, N-&-N1 has been found to induce cell death with better efficacy (5.4-fold ...
Inhibition of CDK4-6 as a novel therapeutic option for neuroblastoma. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Casein Kinase I Isoform Delta (Tau Protein Kinase CSNK1D or CKI Delta or CSNK1D or EC 2.7.11.1 or EC 2.7.11.26) - Pipeline Review, H2 2016 - Market research report and industry analysis - 10293155
Background Over the last decade a number of species, from farm animals to rodents, have been cloned using somatic cell nuclear transfer technology (SCNT). This technique has the potential to revolutionize the way that genetically modified animals are made. In its current state, the process of SCNT is very inefficient (|5% success rate), with several technical and biological hurdles hindering development. Yet, SCNT provides investigators with powerful advantages over other approaches, such as allowing for prescreening for the desired level of transgene expression and eliminating the excess production of undesirable wild-type animals. The rat plays a significant role in biomedical research, but SCNT has been problematic for this species. In this study, we address one aspect of the problem by evaluating methods of activation in artificially constructed rat embryos. Principal Findings We demonstrate that treatment with a calcium ionophore (ionomycin) combined with a variety of cyclin-dependent kinase
Glioblastomas co-opt stem cell regulatory pathways to maintain brain tumor-initiating cells (BTICs), also known as cancer stem cells. NOTCH signaling has been a molecular target in BTICs, but NOTCH antagonists have demonstrated limited efficacy in clinical trials. Recombining binding protein suppressor of hairless (RBPJ) is considered a central transcriptional mediator of NOTCH activity. Here, we report that pharmacologic NOTCH inhibitors were less effective than targeting RBPJ in suppressing tumor growth. While NOTCH inhibitors decreased canonical NOTCH gene expression, RBPJ regulated a distinct profile of genes critical to BTIC stemness and cell cycle progression. RBPJ was preferentially expressed by BTICs and required for BTIC self-renewal and tumor growth. MYC, a key BTIC regulator, bound the ...
p35 is a neuron specific activator of CDK5. The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Activator of TPKII. The complex p35/CDK5 participates in the regulation of the circadian clock by modulating the function of CLOCK protein: phosphorylates CLOCK at Thr-451 and Thr-461 and regulates the transcriptional activity of the CLOCK-ARNTL/BMAL1 heterodimer in association with altered stability and subcellular distribution.
The normal, pyramidal morphology of some of the neurons incdk5 −/− deserves further comment. Analysis of the reeler mutation raised the possibility that disruption of pyramidal morphology and cortical inversion are directly linked. In the cdk5 −/− cerebral cortex, however, the earliest cortical plate neurons are superficial to all later born cells yet still have a pyramidal morphology. One important difference between early cortical plate neurons in reelerand cdk5 −/− mice that may explain this disparity is the normal location of some layer VI cells between the subplate and marginal zone in cdk5 −/−mice. Perhaps only within the environment between subplate and marginal zone can cortical neurons achieve a normal pyramidal morphology. In this position, young neurons would be able to interact with Cajal-Retzius cells of the marginal zone and their secreted factor, reelin. This interaction might then serve as a mechanism to confer a pyramidal morphology.. A persistent question raised ...
Recombinant human CDKN1B protein, fused to His-tag at N-terminus, was expressed in E. coli and purified by using conventional chromatography. MW: 24.2 kDa.
Complete information for CDK5 gene (Protein Coding), Cyclin Dependent Kinase 5, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for CDK18 gene (Protein Coding), Cyclin Dependent Kinase 18, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Rabbit recombinant monoclonal CDK1+Cdk2+Cdk3+Cdk5 antibody [E53] validated for WB, IP, ICC/IF and tested in Human. With 1 independent review.
In Saccharomyces cerevisiae, nutrient levels control multiple cellular processes. Cells lacking the SNF1 gene cannot express glucose-repressible genes and do not accumulate the storage polysaccharide glycogen. The impaired glycogen synthesis is due to maintenance of glycogen synthase in a hyperphosphorylated, inactive state. In a screen for second site suppressors of the glycogen storage defect of snf1 cells, we identified a mutant gene that restored glycogen accumulation and which was allelic with PHO85, which encodes a member of the cyclin-dependent kinase family. In cells with disrupted PHO85 genes, we observed hyperaccumulation of glycogen, activation of glycogen synthase, and impaired glycogen synthase kinase activity. In snf1 cells, glycogen synthase kinase activity was elevated. Partial purification of glycogen synthase kinase activity from yeast extracts resulted in the separation of two fractions by phenyl-Sepharose chromatography, both of which phosphorylated and inactivated glycogen ...
Pathological features of Alzheimers disease (AD) include aggregation of amyloid beta (Aβ) and tau protein. Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, has been implicated in the toxicity of aggregated Aβ. It remains unclear whether MIF affects hyperphosphorylation and aggregation of tau. The effects of MIF deficiency in tau hyperphosphorylation were examined in Mif −/− mice receiving intracerebroventricular (ICV) injection of streptozotocin (STZ) and in APP/PS1 transgenic mice mated with Mif −/− mice. MIF expression and astrocyte activation were evaluated in ICV-STZ mice using immunofluorescence staining. Cultured primary astrocytes were treated with high glucose to mimic STZ function in vitro, and the condition medium (CM) was collected. The level of tau hyperphosphorylation in neurons treated with the astrocyte CM was determined
Although mechanisms of acquired resistance to endocrine therapy have been identified in estrogen receptor-positive (ER+) breast cancer, the causes of intrinsic resistance, present at the time of diagnosis, are less well understood. Haricharan and colleagues linked loss of the MutL mismatch repair (MMR) complex to intrinsic resistance to endocrine therapy. MMR has two damage-sensing complexes: MutS and MutL. In patients with ER+ breast cancer, endocrine therapy resistance was associated with dysregulation of MutL but not MutS. In ER+ breast cancer cell lines, silencing of MutL complex genes promoted resistance to endocrine therapy (including estrogen deprivation, a surrogate for aromatase inhibitor exposure, fulvestrant, and tamoxifen) by preventing CHK2-mediated inhibition of CDK4/6, resulting in deregulated CDK4/6 activity that drove endocrine therapy resistance. Further, mutations that dysregulated MutL promoted resistance to endocrine therapy in patient-derived xenograft models. Response to ...
Introduction: A predominant molecular component analyzed in the study of neurodegenerative diseases is the presence of the Tau-GSK3β complex and its association with protein aggregation into the cell. Several evidences show that GSK3β has an important role in abnormal pattern of the phosphorylation of Tau. However, the molecular events that are governing this complex are unknown. Aim: To determine the effect of 17 β-estradiol treatment on the expression and association of Tau hyperphosphorylation responsible kinases. Methods: 17 β-estradiol treatments were realized in the hippocampus of ovariectomized adult wistar rats and in hippocampal primary cultures treated with β-amiloid. Protein complex association was assessed by co-immunoprecipitation, toxicity assay by LDH release and cell morphologic changes by confocal microscopy. Results: Our results show that 17β-estradiol produced dissociation of macromolecular complexes like Tau/GSK3β, Tau/GluR2/3, Tau/FAK, and Tau/Fyn in hippocampus of ...
Plasmids, recombinant adenoviruses, chemicals, and antibodies. Wild-type and mutated MEF2-dependent luciferase reporter constructs, dominant-negative Cdk5 (dnCdk5), and pcDNA3-MEF2DS444A were described previously (Gong et al., 2003). Recombinant adenoviruses expressing green fluorescent protein (GFP), MEF2D, MEF2DS444A, and dnCdk5 were generated according to He et al. (1998). Polyclonal rabbit antibody specific for a phosphoserine-containing peptide corresponding to a sequence containing SPXR motif found in MEF2s was generated as described previously (Sharma et al., 1999; Gong et al., 2003). Antibodies were purchased from the following vendors: anti-MEF2C and cleaved caspase-3 (Asp175) antibodies from Cell Signaling Technology (Beverly, MA); anti-histone H1, anti-MEF2A, anti-Cdk5, and anti-p35/p25 polyclonal antibodies from Santa Cruz Biotechnology (Santa Cruz, CA); anti-β-actin monoclonal antibody from Sigma (St. Louis, MO); and anti-MEF2D antibody from BD Transduction Laboratories (Lexington, ...
Title: Increased CRMP2 Phosphorylation is Observed in Alzheimers Disease; Does this Tell us Anything About Disease Development?. VOLUME: 6 ISSUE: 3. Author(s):M. P.M. Soutar, P. Thornhill, A. R. Cole and C. Sutherland. Affiliation:Biomedical Research Institute, University of Dundee, Ninewells Hospital, Dundee DD1 9SY, Scotland, United Kingdom.. Abstract: Collapsin response mediator protein-2 (CRMP2) was recently identified as a physiological substrate for GSK3 and Cdk5, two protein kinases suggested to exhibit greater activity in Alzheimer s disease (AD). Indeed, phosphorylation of CRMP2, at the residues targeted by GSK3 and Cdk5, is relatively high in cortex isolated from human AD brain, as well as in the brains of animal models of AD, while phospho-CRMP2 is found in neurofibrillary tangles. In mouse models of AD, increased phosphorylation occurs prior to pathology. Although CRMP2 has no known enzymatic activity, a great deal of information is appearing on its importance in neuronal ...
Schematic of the cell cycle. outer ring: I=Interphase, M=Mitosis; inner ring: M=Mitosis; G1=Gap phase 1; S=Synthesis; G2=Gap phase 2. The duration of mitosis in relation to the other phases has been exaggerated in this diagram Cyclin dependent…
Researchers have identified a subtype of triple-negative breast cancer that may be responsive to inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6), according to findings presented by Asghar et a.... ...
Chromosome, Human, Cancer, Cell Division, Chromatin, PCR, Regulation, RNA, Active Site, Cyclin, Kinases, Cell Cycle, Cyclin-dependent Kinases, and Egg
Find our Crumlin, UK office address, phone number & email id. Contact us if you have any query about our products, service or for any other purpose. Cyclin-dependent kinase inhibitor 1A RCP9477 Product Enquiry
We are looking for a source of Cdk2-GST or Cdk2 to be used in in vitro kinase assays. Can anyone help? Thomas Chiles; e-mail= Thomas.Chiles at bc.edu ...
IMPORTANT NOTE: This forum is not for queries that would otherwise be addressed to a doctor. If you have a question about your condition or treatment please consult your renal unit or doctor. We do not have any editorial or medical resources to answer individual queries ...
IMPORTANT NOTE: This forum is not for queries that would otherwise be addressed to a doctor. If you have a question about your condition or treatment please consult your renal unit or doctor. We do not have any editorial or medical resources to answer individual queries ...
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TY - JOUR. T1 - Dinaciclib induces anaphase catastrophe in lung cancer cells via inhibition of cyclin-dependent kinases 1 and 2. AU - Danilov, Alexey. AU - Hu, Shanhu. AU - Orr, Bernardo. AU - Godek, Kristina. AU - Mustachio, Lisa Maria. AU - Sekula, David. AU - Liu, Xi. AU - Kawakami, Masanori. AU - Johnson, Faye M.. AU - Compton, Duane A.. AU - Freemantle, Sarah J.. AU - Dmitrovsky, Ethan. PY - 2016/11/1. Y1 - 2016/11/1. N2 - Despite advances in targeted therapy, lung cancer remains the most common cause of cancer-related mortality in the United States. Chromosomal instability is a prominent feature in lung cancer and, because it rarely occurs in normal cells, it represents a potential therapeutic target. Our prior work discovered that lung cancer cells undergo anaphase catastrophe in response to inhibition of cyclin-dependent kinase 2 (CDK2), followed by apoptosis and reduced growth. In this study, the effects and mechanisms of the multi-CDK inhibitor dinaciclib on lung cancer cells were ...
Cyclin-dependent kinases (CDKs) are a family of sugar kinases first discovered for their role in regulating the cell cycle. They are also involved in regulating transcription, mRNA processing, and the differentiation of nerve cells. They are present in all known eukaryotes, and their regulatory function in the cell cycle has been evolutionarily conserved. In fact, yeast cells can proliferate normally when their CDK gene has been replaced with the homologous human gene. CDKs are relatively small proteins, with molecular weights ranging from 34 to 40 kDa, and contain little more than the kinase domain. By definition, a CDK binds a regulatory protein called a cyclin. Without cyclin, CDK has little kinase activity; only the cyclin-CDK complex is an active kinase. CDKs phosphorylate their substrates on serines and threonines, so they are serine-threonine kinases. The consensus sequence for the phosphorylation site in the amino acid sequence of a CDK substrate is [S/T*]PX[K/R], where S/T* is the ...
The protein encoded by this gene is a subunit of a heterodimer that, along with SUPT16H, forms chromatin transcriptional elongation factor FACT. FACT interacts specifically with histones H2A/H2B to effect nucleosome disassembly and transcription elongation. FACT and cisplatin-damaged DNA may be crucial to the anticancer mechanism of cisplatin. This encoded protein contains a high mobility group box which most likely constitutes the structure recognition element for cisplatin-modified DNA. This protein also functions as a co-activator of the transcriptional activator p63. An alternatively spliced transcript variant of this gene has been described, but its full-length nature is not known ...
Kim-1-induced kidney injury was associated with reduction of growth of adult fish. Collapsin response mediator protein 3 increases the dendritic arborization of is vidalista 10 generic cialis buy online hippocampal neurons. Angiotensin-converting enzyme inhibition in cardiovascular disease: evidence with perindopril. A ...
The KOMP Repository Collection is located at the MMRRC at the University of California, Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...
Ryu, J. and Lee, C. (2012), Association of glycosylated hemoglobin with the gene encoding CDKAL1 in the Korean Association Resource (KARE) study. Hum. Mutat., 33: 655-659. doi: 10.1002/humu.22040 ...
The prokaryotic adaptive immune system CRISPR/Cas9 has recently been adapted for genome editing in eukaryotic cells. This technique allows for sequence-specific induction of double-strand breaks in genomic DNA of individual cells, effectively resulting in knock-out of targeted genes. It thus promise …
IHCPlus™ KPI-2 / LMTK2 Antibody LS-B8423 is a pathologist validated IHC antibody Rabbit anti-Human KPI-2 / LMTK2. Validated for IF,IHC,Peptide-ELISA,WB. Tested on 20 paraffin-embedded human tissues.
John Carroll One of Pfizers top late-stage prospects is its cancer drug palbociclib, an oral inhibitor of cyclin-dependent kinases (CDK) 4 and 6 that the FDA put in its first group ...
Monoklonale und polyklonale CDK7 Antikörper für viele Methoden. Ausgesuchte Qualitäts-Hersteller für CDK7 Antikörper. Hier bestellen.
Tau兔多克隆抗体(ab97778)可与人样本反应并经WB, IHC实验严格验证。中国75%以上现货,所有产品均提供质保服务,可通过电话、电邮或微信获得本地专属技术支持。
A8326 AZD-5438 AZD5438 is a potent small molecule inhibitor of cyclin-dependent kinase (CDK) 1, 2 and 9 with half maximal inhibitory concentration IC50 of 16 nmol/L, 6 nmol/L and 20 nmol/L respectively. AZD5438 has also been found to potently inhibit the human cyclin E/CDK2 complex, the cyclin B1/CDK1 complex and the cyclin A/CDK2 complex with IC50 of 0.006 μM, 0.016 μM and 0.045 μM respectively. In previous studies, AZD5438 has exhibited significant anti-proliferative activity in a few human tumor cell lines with IC50 ranging from 0.2 μmol/L to 1.7 μmol/L, in which the phosphorylation of a few proteins, including CDK substrates pRb, nucleolin, protein phosphatase 1a and RNA polymerase II COOH-terminal domain, and cell cycling at G2-M, S and G1 phases were inhibited. ...
If you have a question about this talk, please contact Caroline Newnham.. Host: Viji Draviam. Tissue homeostasis in metazoans is regulated by transitions of cells between quiescence and proliferation. The hallmark of proliferating populations is progression through the cell cycle, which is driven by Cyclin-dependent kinase (CDK) activity. I will discuss our recent development of a live-cell sensor for CDK2 activity and the finding that proliferating cells bifurcate into two populations as they exit mitosis. Some cells immediately commit to the next cell cycle by building up CDK2 activity from an intermediate level, while other cells lack CDK2 activity and enter a transient state of quiescence. This bifurcation is directly controlled by the CDK inhibitor p21 and is regulated by mitogens during a restriction window at the end of the previous cell cycle. We are currently exploring the role of cell stress in controlling this bifurcation in an attempt to uncover the root cause of this striking ...
Clone REA756 recognizes the human CD20L, an intracytoplasmic membrane protein, which is also known as Htm4 or MS4A3. It is present specifically in hematopoietic cells and tissues. CD20L functions as a hematopoietic modulator for the G1-S cell cycle transition. It binds to cyclin-dependent kinase inhibitor 3 (CDKN3/KAP) and modulates the level of phosphorylation of cyclin-dependent kinase 2 (CDK2). Additional information: Clone REA756 displays negligible binding to Fc receptors. - Österreich
Revision: 8243 http://svn.sourceforge.net/cdk/?rev=8243&view=rev Author: egonw Date: 2007-04-22 14:13:05 -0700 (Sun, 22 Apr 2007) Log Message: ----------- Use explicit reader instead of ReaderFactory Modified Paths: -------------- trunk/cdk/src/org/openscience/cdk/test/qsar/descriptors/molecular/AutocorrelationDescriptorChargeTest.java trunk/cdk/src/org/openscience/cdk/test/qsar/descriptors/molecular/AutocorrelationDescriptorMassTest.java trunk/cdk/src/org/openscience/cdk/test/qsar/descriptors/molecular/AutocorrelationDescriptorPolarizabilityTest.java trunk/cdk/src/org/openscience/cdk/test/qsar/descriptors/molecular/BCUTDescriptorTest.java trunk/cdk/src/org/openscience/cdk/test/qsar/descriptors/molecular/CPSADescriptorTest.java trunk/cdk/src/org/openscience/cdk/test/qsar/descriptors/molecular/EccentricConnectivityIndexDescriptorTest.java trunk/cdk/src/org/openscience/cdk/test/qsar/descriptors/molecular/GravitationalIndexDescriptorTest.java ...
rs1063192 is a SNP in the cyclin-dependent kinase inhibitor 2B CDKN2B gene. A study of 432 Han Chinese patients with myocardial infarctions concluded that male subjects carrying a rs1063192(C) allele were at 0.71x decreased risk (for MI).[PMID 19272367] Myocardial Infarction ...
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Cdk5r1 - Cyclin-dependent kinase 5 activator - Mus musculus (Mouse) - Cdk5r1 gene & proteinCdk5r1 - Cyclin-dependent kinase 5 activator - Mus musculus (Mouse) - Cdk5r1 gene & protein

Cyclin-dependent kinase 5 activatorUniRule annotation. ,p>Information which has been generated by the UniProtKB automatic ... Belongs to the cyclin-dependent kinase 5 activator family.UniRule annotation. ,p>Information which has been generated by the ... tr,Q542T9,Q542T9_MOUSE Cyclin-dependent kinase 5 activator OS=Mus musculus GN=Cdk5r1 PE=2 SV=1 ... CyclinImported. ,p>Information which has been imported from another database using automatic procedures.,/p> ,p>,a href="/ ...
more infohttp://www.uniprot.org/uniprot/Q542T9

Cyclin-dependent kinase 5 - WikipediaCyclin-dependent kinase 5 - Wikipedia

... membrane-associated neuronal kinase, cyclin-dependent kinase 5/p35-regulated kinase". The Journal of Neuroscience. 23 (12): ... Unlike other cyclin dependent kinases, CDK5 does not also require phosphorylation on the T loop so that binding with the ... Cyclin-Dependent Kinase 5 at the US National Library of Medicine Medical Subject Headings (MeSH) CDK5 human gene location in ... The protein encoded by this gene is part of the cyclin-dependent kinase family. Recently Cdk5 has emerged as an essential ...
more infohttps://en.wikipedia.org/wiki/Cyclin-dependent_kinase_5

Cyclin-Dependent Kinase 5/p35/p39: A Novel and Imminent Therapeutic Target for Diabetes MellitusCyclin-Dependent Kinase 5/p35/p39: A Novel and Imminent Therapeutic Target for Diabetes Mellitus

I. Matsuura and J. H. Wang, "Demonstration of cyclin-dependent kinase inhibitory serine/threonine kinase in bovine thymus," ... D. O. Morgan, "Cyclin-dependent kinases: engines, clocks, and microprocessors," Annual Review of Cell and Developmental Biology ... Cyclin-Dependent Kinase 5/p35/p39: A Novel and Imminent Therapeutic Target for Diabetes Mellitus. Danish Ahmed1 and Manju ... J. Lew, Q. Q. Huang, Z. Qi et al., "A brain-specific activator of cyclin-dependent kinase 5," Nature, vol. 371, no. 6496, pp. ...
more infohttps://www.hindawi.com/journals/ije/2011/530274/ref/

CDK5R1 - Cyclin-dependent kinase 5 activator 1 precursor - Homo sapiens (Human) - CDK5R1 gene & proteinCDK5R1 - Cyclin-dependent kinase 5 activator 1 precursor - Homo sapiens (Human) - CDK5R1 gene & protein

Cyclin-dependent kinase 5 activator 1, p35: *. Plasma membrane. *Cell membrane Curated; Lipid-anchor Curated; Cytoplasmic side ... Cyclin-dependent kinase 5 activator 1, p35Add BLAST. 306. ,p>This subsection of the PTM / Processing section describes the ... Cyclin-dependent kinase 5 activator 1, p25Add BLAST. 209. Amino acid modifications. Feature key. Position(s). Description ... "Cyclin-dependent kinase 5 (Cdk5) regulates the function of CLOCK protein by direct phosphorylation.". Kwak Y., Jeong J., Lee S. ...
more infohttp://www.uniprot.org/uniprot/Q15078

Cyclin-Dependent Kinase 5-Deficient Mice Demonstrate Novel Developmental Arrest in Cerebral Cortex | Journal of NeuroscienceCyclin-Dependent Kinase 5-Deficient Mice Demonstrate Novel Developmental Arrest in Cerebral Cortex | Journal of Neuroscience

1994) Neuronal cdc2-like kinase is a complex of cyclin-dependent kinase 5 and a novel brain-specific regulatory subunit. Nature ... threonine kinase originally cloned via its homology to other cyclin dependent kinases (Hellmich et al., 1992; Lew et al., 1992 ... Cyclin-Dependent Kinase 5-Deficient Mice Demonstrate Novel Developmental Arrest in Cerebral Cortex. Edward C. Gilmore, Toshio ... The cerebral cortex of mice with a targeted disruption in the gene for cyclin-dependent kinase 5 (cdk5) is abnormal in its ...
more infohttp://www.jneurosci.org/content/18/16/6370?ijkey=b68f7f83b5164f13f8a3773b75bb13b0652ae3d1&keytype2=tf_ipsecsha

Cyclin-Dependent Kinase 5 Mediates Neurotoxin-Induced Degradation of the Transcription Factor Myocyte Enhancer Factor 2 |...Cyclin-Dependent Kinase 5 Mediates Neurotoxin-Induced Degradation of the Transcription Factor Myocyte Enhancer Factor 2 |...

Calpain-dependent proteolytic cleavage of the p35 cyclin-dependent kinase 5 activator to p25. J Biol Chem 275: 17166-17172. ... Cyclin-Dependent Kinase 5 Mediates Neurotoxin-Induced Degradation of the Transcription Factor Myocyte Enhancer Factor 2. Xiaoli ... Li BS, Zhang L, Takahashi S, Ma W, Jaffe H, Kulkarni AB, Pant HC (2002) Cyclin-dependent kinase 5 prevents neuronal apoptosis ... Bajaj NP, Al-Sarraj ST, Anderson V, Kibble M, Leigh N, Miller CC (1998) Cyclin-dependent kinase-5 is associated with lipofuscin ...
more infohttp://www.jneurosci.org/content/25/19/4823.long

Frontiers | Inducible Knockout of the Cyclin-Dependent Kinase 5 Activator p35 Alters Hippocampal Spatial Coding and Neuronal...Frontiers | Inducible Knockout of the Cyclin-Dependent Kinase 5 Activator p35 Alters Hippocampal Spatial Coding and Neuronal...

Inducible deletion of the p35 gene in adult mice results in profound deficits in hippocampal-dependent spatial learning and ... Inducible deletion of the p35 gene in adult mice results in profound deficits in hippocampal-dependent spatial learning and ... p35 is an activating co-factor of Cyclin-dependent kinase 5, a protein whose dysfunction has been implicated in a wide-range of ... p35 is an activating co-factor of Cyclin-dependent kinase 5 (Cdk5), a protein whose dysfunction has been implicated in a wide- ...
more infohttps://www.frontiersin.org/articles/10.3389/fncel.2018.00138/full

Effects of Glycogen Synthase Kinase 3β and Cyclin-Dependent Kinase 5 Inhibitors on Morphine-Induced Analgesia and Tolerance in...Effects of Glycogen Synthase Kinase 3β and Cyclin-Dependent Kinase 5 Inhibitors on Morphine-Induced Analgesia and Tolerance in...

Effects of Glycogen Synthase Kinase 3β and Cyclin-Dependent Kinase 5 Inhibitors on Morphine-Induced Analgesia and Tolerance in ... Effects of Glycogen Synthase Kinase 3β and Cyclin-Dependent Kinase 5 Inhibitors on Morphine-Induced Analgesia and Tolerance in ... Effects of Glycogen Synthase Kinase 3β and Cyclin-Dependent Kinase 5 Inhibitors on Morphine-Induced Analgesia and Tolerance in ... Effects of Glycogen Synthase Kinase 3β and Cyclin-Dependent Kinase 5 Inhibitors on Morphine-Induced Analgesia and Tolerance in ...
more infohttp://jpet.aspetjournals.org/content/319/2/832/tab-figures-data

Cyclin-dependent-like kinase 5 (Q00535) | InterPro | EMBL-EBICyclin-dependent-like kinase 5 (Q00535) | 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.
more infohttp://www.ebi.ac.uk/interpro/protein/Q00535

Regulation of Cyclin-Dependent Kinase 5 and Calcium/Calmodulin-Dependent Protein Kinase II by Phosphatidylinositol-Linked...Regulation of Cyclin-Dependent Kinase 5 and Calcium/Calmodulin-Dependent Protein Kinase II by Phosphatidylinositol-Linked...

ABBREVIATIONS: PKA, protein kinase A; PLCβ, phospholipase Cβ; cdk5, cyclin-dependent kinase 5; CaMK II, calcium/calmodulin- ... and dose-dependent stimulations of cyclin-dependent kinase 5 (cdk5) and calcium/calmodulin-dependent protein kinase II (CaMK II ... Liu F, Ma XH, Ule J, Bibb JA, Nishi A, Demaggio AJ, Yan Z, Nairm AC, and Greengard (2001) Regulation of cyclin-dependent kinase ... Dhavan R, Greer PL, Morabito MA, Orlando LR, and Tsai LH (2002) The cyclin-dependent kinase 5 activators p35 and p39 interact ...
more infohttp://molpharm.aspetjournals.org/content/66/6/1500

Homo sapiens cyclin dependent kinase like 5 (CDKL5), transcript varian - Nucleotide - NCBIHomo sapiens cyclin dependent kinase like 5 (CDKL5), transcript varian - Nucleotide - NCBI

Homo sapiens cyclin dependent kinase like 5 (CDKL5), transcript variant I, mRNA Homo sapiens cyclin dependent kinase like 5 ( ... Homo sapiens cyclin dependent kinase like 5 (CDKL5), transcript variant I, mRNA. NCBI Reference Sequence: NM_003159.2 ... See the reference protein sequence for cyclin-dependent kinase-like 5 isoform 1 (NP_003150.1). ... CDKL Family Kinases Have Evolved Distinct Structural Features and Ciliary Function. [Cell Rep. 2018] CDKL Family Kinases Have ...
more infohttps://www.ncbi.nlm.nih.gov/nuccore/NM_003159

Cyclin-dependent kinase 5 activity regulates pain signaling.Cyclin-dependent kinase 5 activity regulates pain signaling.

... Academic Article * Authors Version ... Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase implicated in the development and disease of the ... The precise role of this kinase in sensory pathways has not been well characterized. Here we report a molecular role for Cdk5 ...
more infohttp://vivo.mblwhoilibrary.org/display/publication44482

Cyclin-dependent kinase 5 modulates nociceptive signaling through direct phosphorylation of transient receptor potential...Cyclin-dependent kinase 5 modulates nociceptive signaling through direct phosphorylation of transient receptor potential...

Cyclin-dependent kinase 5 modulates nociceptive signaling through direct phosphorylation of transient receptor potential ... We have previously reported that cyclin-dependent kinase 5 (Cdk5) activity regulates nociceptive signaling. In this article we ... Cyclin-dependent kinase 5 modulates nociceptive signaling through direct phosphorylation of transient receptor potential ...
more infohttp://scholarbank.nus.edu.sg/handle/10635/120809

A CYCLIN DEPENDENT KINASE-5 INHIBITORS: SYNTHESIS AND SAR OF CLUBBED TRIAZOLE.A CYCLIN DEPENDENT KINASE-5 INHIBITORS: SYNTHESIS AND SAR OF CLUBBED TRIAZOLE.

... Rajendra Dnyandeo Dighe*, Mahendra Ramesh ... method and examine for their cyclin dependent kinase-5 (cdk5) inhibitors, potentially useful for treatment of Alzheimer disease ...
more infohttp://www.ajptr.com/archive/volume-2/february-2012-issue-1/article-101.html

Cyclin-dependent kinase 5-mediated phosphorylation of CHIP promotes the tAIF-dependent death pathway in rotenone-treated...Cyclin-dependent kinase 5-mediated phosphorylation of CHIP promotes the tAIF-dependent death pathway in rotenone-treated...

Kim, C., Lee, J., Ko, Y. U., & Oh, Y. J. (2018). Cyclin-dependent kinase 5-mediated phosphorylation of CHIP promotes the tAIF- ... N2 - Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase. Its dysregulation has been implicated in ... AB - Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase. Its dysregulation has been implicated in ... Kim, C, Lee, J, Ko, YU & Oh, YJ 2018, Cyclin-dependent kinase 5-mediated phosphorylation of CHIP promotes the tAIF-dependent ...
more infohttps://yonsei.pure.elsevier.com/en/publications/cyclin-dependent-kinase-5-mediated-phosphorylation-of-chip-promot

Refubium - Cyclin-dependent kinase 5 regulatory subunit-associated protein 2 (Cdk5rap2)
in neuronal differentiation and germ...Refubium - Cyclin-dependent kinase 5 regulatory subunit-associated protein 2 (Cdk5rap2) in neuronal differentiation and germ...

Cyclin-dependent kinase 5 regulatory subunit-associated protein 2 (Cdk5rap2) in neuronal differentiation and germ cell pool ... Cyclin-dependent kinase 5 regulatory subunit-associated protein 2 (Cdk5rap2) in neuronal differentiation and germ cell pool ... Cyclin-dependent kinase 5 regulatory subunit-associated protein 2 (Cdk5rap2) in neuronal differentiation and germ cell pool ... Die Rolle von Cyclin-dependent kinase 5 regulatory subunit-associated protein 2 (Cdk5rap2) bezüglich der neuronalen ...
more infohttps://refubium.fu-berlin.de/handle/fub188/6443?locale-attribute=de

Inhibition of cyclin-dependent kinase 5 affects early neuroinflammatory signalling in murine model of amyloid beta toxicity |...Inhibition of cyclin-dependent kinase 5 affects early neuroinflammatory signalling in murine model of amyloid beta toxicity |...

... belongs to the family of proline-directed serine/threonine kinases and plays a critical role in neuronal differentiation, ... clearly show the involvement of Cdk5 in modulation of brain inflammatory response induced by Aβ and may indicate this kinase as ... Brooks G. Cyclin-dependent kinases and cyclin-dependent kinase inhibitors. Detection methods and activity measurements. Methods ... Liu C, Zhai X, Zhao B, Wang Y, Xu Z. Cyclin I-like (CCNI2) is a cyclin-dependent kinase 5 (CDK5) activator and is involved in ...
more infohttps://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-017-1027-y

Cyclin-dependent kinase 5 acts as a critical determinant of AKT-dependent proliferation and regulates differential gene...Cyclin-dependent kinase 5 acts as a critical determinant of AKT-dependent proliferation and regulates differential gene...

2015). Cyclin-dependent kinase 5 acts as a critical determinant of AKT-dependent proliferation and regulates differential gene ... Cyclin-dependent kinase 5 acts as a critical determinant of AKT-dependent proliferation and regulates differential gene ... Contrary to cell cycle-associated cyclin-dependent kinases, CDK5 is best known for its regulation of signaling processes in ...
more infohttps://erepo.uef.fi/handle/123456789/42

p35/cyclin-dependent kinase 5 phosphorylation of ras guanine nucleotide releasing factor 2 (RasGRF2) mediates Rac-dependent...p35/cyclin-dependent kinase 5 phosphorylation of ras guanine nucleotide releasing factor 2 (RasGRF2) mediates Rac-dependent...

Cyclin-dependent kinase 5 (Cdk5) is a proline-directed kinase the activity of which is dependent on association with its neuron ... p35/cyclin-dependent kinase 5 phosphorylation of ras guanine nucleotide releasing factor 2 (RasGRF2) mediates Rac-dependent ... Extracellular Signal-regulated kinase 1/2 activity, altering RasGRF2 and microtubule-associated protein 1b distribution in ... to a decrease in Rac-guanidine exchange factor activity and a subsequent reduction in extracellular signal-regulated kinase 1/2 ...
more infohttp://vivo.mblwhoilibrary.org/display/publication44420

Cyclin-dependent kinase 5 acts as a critical determinant of AKT-dependent proliferation and regulates differential gene...Cyclin-dependent kinase 5 acts as a critical determinant of AKT-dependent proliferation and regulates differential gene...

Artur » Lista över publikationer » Cyclin-dependent kinase 5 acts as a critical determinant of AKT-dependent proliferation and ... Cyclin-dependent kinase 5 acts as a critical determinant of AKT-dependent proliferation and regulates differential gene ... Contrary to cell cycle-associated cyclin-dependent kinases, CDK5 is best known for its regulation of signaling processes in ... However, the amplified cell growth was found to be separated from AR signaling, further corroborated by CDK5-dependent ...
more infohttp://research.abo.fi/converis/portal/Publication/959162?lang=sv_SE

Cyclin-dependent-like kinase 5Cyclin-dependent-like kinase 5

This gene encodes a proline-directed serine/threonine kinase that is a member of the cyclin-dependent kinase family of proteins ... Interacts with D1 and D3-type G1 cyclins. Phosphorylates SRC, NOS3, VIM/vimentin, p35/CDK5R1, MEF2A, SIPA1L1, SH3GLB1, PXN, ... Proline-directed serine/threonine-protein kinase essential for neuronal cell cycle arrest and differentiation and may be ... SRC phosphorylation mediates its ubiquitin-dependent degradation and thus leads to cytoskeletal reorganization. May regulate ...
more infohttps://pharos.nih.gov/idg/targets/Q00535

Alterations in cyclin-dependent protein kinase 5 (CDK5) protein levels, activity and immunocytochemistry in canine motor neuron...Alterations in cyclin-dependent protein kinase 5 (CDK5) protein levels, activity and immunocytochemistry in canine motor neuron...

Green, S. L., Vulliet, P. R., Pinter, M. J., & Cork, L. C. (1998). Alterations in cyclin-dependent protein kinase 5 (CDK5) ... Cyclin- dependent kinase 5 (CDK5), a kinase related to the cell cycle kinase cdc2, phosphorylates neurofilaments and regulates ... Green, Sherril L. ; Vulliet, Philip R ; Pinter, Martin J. ; Cork, Linda C. / Alterations in cyclin-dependent protein kinase 5 ( ... Cyclin- dependent kinase 5 (CDK5), a kinase related to the cell cycle kinase cdc2, phosphorylates neurofilaments and regulates ...
more infohttps://ucdavis.pure.elsevier.com/en/publications/alterations-in-cyclin-dependent-protein-kinase-5-cdk5-protein-lev

Neurofibrillary tangle - WikipediaNeurofibrillary tangle - Wikipedia

Cyclin-dependent kinase 5[edit]. Cyclin-dependent kinase 5 (CDK5) is a kinase that has been previously hypothesized to ... A protein called kinase p38γ phosphorylates tau at the threonine-205 amino acid. The activity of this gamma kinase enzyme is ... It was found that the degree of tau pathology was dependent on time and the level of gene expression.[3] Groups receiving a ... As well as lead encephalopathy, tuberous sclerosis, Pantothenate kinase-associated neurodegeneration, and lipofuscinosis[28] ...
more infohttps://en.wikipedia.org/wiki/Neurofibrillary_tangle

CDK5 Gene - GeneCards | CDK5 Protein | CDK5 AntibodyCDK5 Gene - GeneCards | CDK5 Protein | CDK5 Antibody

Cyclin Dependent Kinase 5, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human ... protein serine/threonine kinase activity. TAS. --. GO:0004693. cyclin-dependent protein serine/threonine kinase activity. TAS. ... Cdks (cyclin-dependent kinases) are heteromeric serine/threonine kinases that control progression through the cell cycle in ... This gene encodes a proline-directed serine/threonine kinase that is a member of the cyclin-dependent kinase family of proteins ...
more infohttp://www.genecards.org/cgi-bin/carddisp.pl?gene=CDK5&snp=69

CDK5R1 Gene - GeneCards | CD5R1 Protein | CD5R1 AntibodyCDK5R1 Gene - GeneCards | CD5R1 Protein | CD5R1 Antibody

Cyclin Dependent Kinase 5 Regulatory Subunit 1, including: function, proteins, disorders, pathways, orthologs, and expression. ... p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5. (PMID: 8090221) Tsai LH … Harlow E (Nature 1994) 2 3 ... regulation of cyclin-dependent protein serine/threonine kinase activity. TAS. 7592934. GO:0000226. microtubule cytoskeleton ... Cyclin-dependent kinase 5 activator 1. Protein Accession:. Q15078. Secondary Accessions: *E1P664 ...
more infohttps://www.genecards.org/cgi-bin/carddisp.pl?gene=CDK5R1&keywords=GH17J032489&prefilter=genomic_location
  • In the current study, we have elucidated a mechanism whereby protein phosphatase 2A (PP2A) is activated by a cAMP/PKA-dependent pathway, leading to dephosphorylation of Thr-75. (pnas.org)
  • In a positive feedback loop, ephrin-B-dependent EPHB2 activation stimulates the HRAS-Erk pathway, and the increase in Mek and/or Erk activity in turn enables enhanced responsiveness of EPHB2 to ephrin-B stimulation through unknown mechanisms. (nih.gov)
  • In neurons, ephrin-As can use the p75 nerve growth factor receptor as a signaling partner to activate the FYN Src family kinase. (nih.gov)
  • While these animals were found to have deficiencies in hippocampal-dependent spatial learning and alterations in in vitro synaptic plasticity, interpretation of these phenotypes is complicated as a result of the changes in the gross anatomy. (frontiersin.org)
  • The Eph receptor tyrosine kinases and their ephrin ligands have intriguing expression patterns in cancer cells and tumour blood vessels, which suggest important roles for their bidirectional signals in many aspects of cancer development and progression. (nih.gov)