A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation.
A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin.
Transforming proteins coded by sis oncogenes. Transformation of cells by v-sis is related to its interaction with the PDGF receptor and also its ability to alter other transcription factors.
The GENETIC TRANSLATION product from a GENE FUSION between a sequence from the tpr protein gene on the human CHROMOSOME 1 and the gene for PROTO-ONCOGENE PROTEINS C-MET.
An oncogene protein that was originally isolated from a spontaneous musculo-aponeurotic FIBROSARCOMA in CHICKEN and shown to be the transforming gene of the avian retrovirus AS42. It is a basic leucine zipper TRANSCRIPTION FACTOR and the founding member of the MAF TRANSCRIPTION FACTORS.
An absence or deficiency in PROTEIN C which leads to impaired regulation of blood coagulation. It is associated with an increased risk of severe or premature thrombosis. (Stedman's Med. Dict., 26th ed.)
Transforming glycoprotein coded by the fms oncogene from the Susan McDonough strain of feline sarcoma virus (SM-FeSV). The oncogene protein v-fms lacks sequences, which, in the highly homologous proto-oncogene protein c-fms (CSF-1 receptor), normally serve to regulate its tyrosine kinase activity. The missing sequences in v-fms mimic the effect of ligand and lead to constitutive cell growth. The protein gp120(v-fms) is post-translationally modified to generate gp140(v-fms).
Transforming proteins coded by mos oncogenes. The v-mos proteins were originally isolated from the Moloney murine sarcoma virus (Mo-MSV).
A member of the serpin family of proteins that is found in plasma and urine. It is dependent on heparin and is able to inhibit activated PROTEIN C; THROMBIN; KALLIKREIN; and other SERINE ENDOPEPTIDASES.
Transforming protein coded by myc oncogenes. The v-myc protein has been found in several replication-defective avian retrovirus isolates which induce a broad spectrum of malignancies.
Transforming protein coded by jun oncogenes (GENES, JUN). This is a gag-onc fusion protein of about 65 kDa derived from avian sarcoma virus. v-jun lacks a negative regulatory domain that regulates transcription in c-jun.
A family of transforming proteins isolated from retroviruses such as MOUSE SARCOMA VIRUSES. They are viral-derived members of the raf-kinase family of serine-theonine kinases.
Transforming proteins coded by fos oncogenes. These proteins have been found in the Finkel-Biskis-Jinkins (FBJ-MSV) and Finkel-Biskis-Reilly (FBR-MSV) murine sarcoma viruses which induce osteogenic sarcomas in mice. The FBJ-MSV v-fos gene encodes a p55-kDa protein and the FBR-MSV v-fos gene encodes a p75-kDa fusion protein.
A hemostatic disorder characterized by a poor anticoagulant response to activated protein C (APC). The activated form of Factor V (Factor Va) is more slowly degraded by activated protein C. Factor V Leiden mutation (R506Q) is the most common cause of APC resistance.
A signal transducing adaptor protein that is encoded by the crk ONCOGENE from TYPE C AVIAN RETROVIRUSES. It contains SRC HOMOLOGY DOMAINS and is closely related to its cellular homolog, PROTO-ONCOGENE PROTEIN C-CRK.
Transforming proteins coded by myb oncogenes. Transformation of cells by v-myb in conjunction with v-ets is seen in the avian E26 leukemia virus.
An oncoprotein from the Cas NS-1 murine retrovirus that induces pre- B-CELL LYMPHOMA and MYELOID LEUKEMIAS. v-cbl protein is a tyrosine-phosphorylated, truncated form of its cellular homologue, PROTO-ONCOGENE PROTEIN C-CBL.
Transforming proteins encoded by erbB oncogenes from the avian erythroblastosis virus. The protein is a truncated form of the EGF receptor (RECEPTOR, EPIDERMAL GROWTH FACTOR) whose kinase domain is constitutively activated by deletion of the ligand-binding domain.
Transforming proteins encoded by the abl oncogenes. Oncogenic transformation of c-abl to v-abl occurs by insertional activation that results in deletions of specific N-terminal amino acids.
Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of "v-" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix "c-" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene.
Transforming proteins coded by rel oncogenes. The v-rel protein competes with rel-related proteins and probably transforms cells by acting as a dominant negative version of c-rel. This results in the induction of a broad range of leukemias and lymphomas.
The vitamin K-dependent cofactor of activated PROTEIN C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S; (PROTEIN S DEFICIENCY); can lead to recurrent venous and arterial thrombosis.
Transforming proteins encoded by erbA oncogenes from the avian erythroblastosis virus. They are truncated versions of c-erbA, the thyroid hormone receptor (RECEPTORS, THYROID HORMONE) that have retained both the DNA-binding and hormone-binding domains. Mutations in the hormone-binding domains abolish the transcriptional activation function. v-erbA acts as a dominant repressor of c-erbA, inducing transformation by disinhibiting proliferation.
A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation.
Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).
Transforming protein encoded by ras oncogenes. Point mutations in the cellular ras gene (c-ras) can also result in a mutant p21 protein that can transform mammalian cells. Oncogene protein p21(ras) has been directly implicated in human neoplasms, perhaps accounting for as much as 15-20% of all human tumors. This enzyme was formerly listed as EC
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.
Endogenous substances, usually proteins, that are involved in the blood coagulation process.
A pulmonary surfactant associated protein that plays a role in alveolar stability by lowering the surface tension at the air-liquid interface. It is a membrane-bound protein that constitutes 1-2% of the pulmonary surfactant mass. Pulmonary surfactant-associated protein C is one of the most hydrophobic peptides yet isolated and contains an alpha-helical domain with a central poly-valine segment that binds to phospholipid bilayers.
A viral oncoprotein originally isolated from a murine T CELL LYMPHOMA infected with the acutely transforming retrovirus AKT8. v-akt protein is the viral homologue of PROTO-ONCOGENE PROTEINS C-AKT.
Heat- and storage-labile plasma glycoprotein which accelerates the conversion of prothrombin to thrombin in blood coagulation. Factor V accomplishes this by forming a complex with factor Xa, phospholipid, and calcium (prothrombinase complex). Deficiency of factor V leads to Owren's disease.
A tyrosine-specific protein kinase encoded by the v-src oncogene of ROUS SARCOMA VIRUS. The transforming activity of pp60(v-src) depends on both the lack of a critical carboxy-terminal tyrosine phosphorylation site at position 527, and the attachment of pp60(v-src) to the plasma membrane which is accomplished by myristylation of its N-terminal glycine.
Activated form of factor V. It is an essential cofactor for the activation of prothrombin catalyzed by factor Xa.
An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN.
Products of viral oncogenes, most commonly retroviral oncogenes. They usually have transforming and often protein kinase activities.
The process of the interaction of BLOOD COAGULATION FACTORS that results in an insoluble FIBRIN clot.
Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein.
The GENETIC TRANSLATION products of the fusion between an ONCOGENE and another gene. The latter may be of viral or cellular origin.
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia.
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.
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.
An autosomal dominant disorder showing decreased levels of plasma protein S antigen or activity, associated with venous thrombosis and pulmonary embolism. PROTEIN S is a vitamin K-dependent plasma protein that inhibits blood clotting by serving as a cofactor for activated PROTEIN C (also a vitamin K-dependent protein), and the clinical manifestations of its deficiency are virtually identical to those of protein C deficiency. Treatment with heparin for acute thrombotic processes is usually followed by maintenance administration of coumarin drugs for the prevention of recurrent thrombosis. (From Harrison's Principles of Internal Medicine, 12th ed, p1511; Wintrobe's Clinical Hematology, 9th ed, p1523)
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.
Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.
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.
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.
A family of proteinase-activated receptors that are specific for THROMBIN. They are found primarily on PLATELETS and on ENDOTHELIAL CELLS. Activation of thrombin receptors occurs through the proteolytic action of THROMBIN, which cleaves the N-terminal peptide from the receptor to reveal a new N-terminal peptide that is a cryptic ligand for the receptor. The receptors signal through HETEROTRIMERIC GTP-BINDING PROTEINS. Small synthetic peptides that contain the unmasked N-terminal peptide sequence can also activate the receptor in the absence of proteolytic activity.
A disorder of HEMOSTASIS in which there is a tendency for the occurrence of THROMBOSIS.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Hemorrhagic and thrombotic disorders that occur as a consequence of abnormalities in blood coagulation due to a variety of factors such as COAGULATION PROTEIN DISORDERS; BLOOD PLATELET DISORDERS; BLOOD PROTEIN DISORDERS or nutritional conditions.
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.
Established cell cultures that have the potential to propagate indefinitely.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide 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.
The time required for the appearance of FIBRIN strands following the mixing of PLASMA with phospholipid platelet substitute (e.g., crude cephalins, soybean phosphatides). It is a test of the intrinsic pathway (factors VIII, IX, XI, and XII) and the common pathway (fibrinogen, prothrombin, factors V and X) of BLOOD COAGULATION. It is used as a screening test and to monitor HEPARIN therapy.
A thrombin receptor subtype that couples to HETEROTRIMERIC GTP-BINDING PROTEINS resulting in the activation of a variety of signaling mechanisms including decreased intracellular CYCLIC AMP, increased TYPE C PHOSPHOLIPASES and increased PHOSPHOLIPASE A2.
A cell line derived from cultured tumor cells.
Agents that prevent clotting.
Proteins prepared by recombinant DNA technology.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
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.
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.
Activated form of factor X that participates in both the intrinsic and extrinsic pathways of blood coagulation. It catalyzes the conversion of prothrombin to thrombin in conjunction with other cofactors.
Found in various tissues, particularly in four blood-clotting proteins including prothrombin, in kidney protein, in bone protein, and in the protein present in various ectopic calcifications.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
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.
Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Proto-oncogenes have names of the form c-onc.
Laboratory tests for evaluating the individual's clotting mechanism.
A disorder characterized by procoagulant substances entering the general circulation causing a systemic thrombotic process. The activation of the clotting mechanism may arise from any of a number of disorders. A majority of the patients manifest skin lesions, sometimes leading to PURPURA FULMINANS.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
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.
A plasma alpha 2 glycoprotein that accounts for the major antithrombin activity of normal plasma and also inhibits several other enzymes. It is a member of the serpin superfamily.
Formation and development of a thrombus or blood clot in the blood vessel.
Inflammation of a vein associated with a blood clot (THROMBUS).
A deficiency of blood coagulation factor V (known as proaccelerin or accelerator globulin or labile factor) leading to a rare hemorrhagic tendency known as Owren's disease or parahemophilia. It varies greatly in severity. Factor V deficiency is an autosomal recessive trait. (Dorland, 27th ed)
Family of retrovirus-associated DNA sequences (myc) originally isolated from an avian myelocytomatosis virus. The proto-oncogene myc (c-myc) codes for a nuclear protein which is involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Truncation of the first exon, which appears to regulate c-myc expression, is crucial for tumorigenicity. The human c-myc gene is located at 8q24 on the long arm of chromosome 8.
Storage-stable glycoprotein blood coagulation factor that can be activated to factor Xa by both the intrinsic and extrinsic pathways. A deficiency of factor X, sometimes called Stuart-Prower factor deficiency, may lead to a systemic coagulation disorder.
Cellular DNA-binding proteins encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis.
Cellular proteins encoded by the H-ras, K-ras and N-ras genes. The proteins have GTPase activity and are involved in signal transduction as monomeric GTP-binding proteins. Elevated levels of p21 c-ras have been associated with neoplasia. This enzyme was formerly listed as EC
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Endogenous factors and drugs that directly inhibit the action of THROMBIN, usually by blocking its enzymatic activity. They are distinguished from INDIRECT THROMBIN INHIBITORS, such as HEPARIN, which act by enhancing the inhibitory effects of antithrombins.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Retroviral proteins that have the ability to transform cells. They can induce sarcomas, leukemias, lymphomas, and mammary carcinomas. Not all retroviral proteins are oncogenic.
The process which spontaneously arrests the flow of BLOOD from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements (eg. ERYTHROCYTE AGGREGATION), and the process of BLOOD COAGULATION.
Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by HYPOTENSION despite adequate fluid infusion, it is called SEPTIC SHOCK.
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.
Transport proteins that carry specific substances in the blood or across cell membranes.
Activated form of factor VIII. The B-domain of factor VIII is proteolytically cleaved by thrombin to form factor VIIIa. Factor VIIIa exists as a non-covalent dimer in a metal-linked (probably calcium) complex and functions as a cofactor in the enzymatic activation of factor X by factor IXa. Factor VIIIa is similar in structure and generation to factor Va.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
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.
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.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
A severe, rapidly fatal reaction occurring most commonly in children following an infectious illness. It is characterized by large, rapidly spreading skin hemorrhages, fever, or shock. Purpura fulminans often accompanies or is triggered by DISSEMINATED INTRAVASCULAR COAGULATION.
An absence or reduced level of Antithrombin III leading to an increased risk for thrombosis.
The rate dynamics in chemical or physical systems.
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.
A lipid phosphatase that acts on phosphatidylinositol-3,4,5-trisphosphate to regulate various SIGNAL TRANSDUCTION PATHWAYS. It modulates CELL GROWTH PROCESSES; CELL MIGRATION; and APOPTOSIS. Mutations in PTEN are associated with COWDEN DISEASE and PROTEUS SYNDROME as well as NEOPLASTIC CELL TRANSFORMATION.
Constituent composed of protein and phospholipid that is widely distributed in many tissues. It serves as a cofactor with factor VIIa to activate factor X in the extrinsic pathway of blood coagulation.
A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.
The natural enzymatic dissolution of FIBRIN.
An inheritable change in cells manifested by changes in cell division and growth and alterations in cell surface properties. It is induced by infection with a transforming virus.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
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.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). This enzyme was formerly listed as EC
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.
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.
Activated form of factor VII. Factor VIIa activates factor X in the extrinsic pathway of blood coagulation.
Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.
Protein-lipid combinations abundant in brain tissue, but also present in a wide variety of animal and plant tissues. In contrast to lipoproteins, they are insoluble in water, but soluble in a chloroform-methanol mixture. The protein moiety has a high content of hydrophobic amino acids. The associated lipids consist of a mixture of GLYCEROPHOSPHATES; CEREBROSIDES; and SULFOGLYCOSPHINGOLIPIDS; while lipoproteins contain PHOSPHOLIPIDS; CHOLESTEROL; and TRIGLYCERIDES.
A lipid cofactor that is required for normal blood clotting. Several forms of vitamin K have been identified: VITAMIN K 1 (phytomenadione) derived from plants, VITAMIN K 2 (menaquinone) from bacteria, and synthetic naphthoquinone provitamins, VITAMIN K 3 (menadione). Vitamin K 3 provitamins, after being alkylated in vivo, exhibit the antifibrinolytic activity of vitamin K. Green leafy vegetables, liver, cheese, butter, and egg yolk are good sources of vitamin K.
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.
The formation or presence of a blood clot (THROMBUS) within a vein.
Substances, usually endogenous, that act as inhibitors of blood coagulation. They may affect one or multiple enzymes throughout the process. As a group, they also inhibit enzymes involved in processes other than blood coagulation, such as those from the complement system, fibrinolytic enzyme system, blood cells, and bacteria.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.
Hemorrhagic and thrombotic disorders resulting from abnormalities or deficiencies of coagulation proteins.
A cell surface protein-tyrosine kinase receptor that is overexpressed in a variety of ADENOCARCINOMAS. It has extensive homology to and heterodimerizes with the EGF RECEPTOR, the ERBB-3 RECEPTOR, and the ERBB-4 RECEPTOR. Activation of the erbB-2 receptor occurs through heterodimer formation with a ligand-bound erbB receptor family member.
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.
Substances and drugs that lower the SURFACE TENSION of the mucoid layer lining the PULMONARY ALVEOLI.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
The erbB-2 gene is a proto-oncogene that codes for the erbB-2 receptor (RECEPTOR, ERBB-2), a protein with structural features similar to the epidermal growth factor receptor. Its name originates from the viral oncogene homolog (v-erbB) which is a truncated form of the chicken erbB gene found in the avian erythroblastosis virus. Overexpression and amplification of the gene is associated with a significant number of adenocarcinomas. The human c-erbB-2 gene is located at 17q21.2.
Heat- and storage-stable plasma protein that is activated by tissue thromboplastin to form factor VIIa in the extrinsic pathway of blood coagulation. The activated form then catalyzes the activation of factor X to factor Xa.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
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.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
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.
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).
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.
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.
A metallocarboxypeptidase that removes C-terminal lysine and arginine from biologically active peptides and proteins thereby regulating their activity. It is a zinc enzyme with no preference shown for lysine over arginine. Pro-carboxypeptidase U in human plasma is activated by thrombin or plasmin during clotting to form the unstable carboxypeptidase U.
A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.
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.
Obstruction of a blood vessel (embolism) by a blood clot (THROMBUS) in the blood stream.
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.
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.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
Clotting time of PLASMA mixed with a THROMBIN solution. It is a measure of the conversion of FIBRINOGEN to FIBRIN, which is prolonged by AFIBRINOGENEMIA, abnormal fibrinogen, or the presence of inhibitory substances, e.g., fibrin-fibrinogen degradation products, or HEPARIN. BATROXOBIN, a thrombin-like enzyme unaffected by the presence of heparin, may be used in place of thrombin.
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.
Blood-coagulation factor VIII. Antihemophilic factor that is part of the factor VIII/von Willebrand factor complex. Factor VIII is produced in the liver and acts in the intrinsic pathway of blood coagulation. It serves as a cofactor in factor X activation and this action is markedly enhanced by small amounts of thrombin.
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.
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.
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.
Elements of limited time intervals, contributing to particular results or situations.
An antiphospholipid antibody found in association with systemic lupus erythematosus (LUPUS ERYTHEMATOSUS, SYSTEMIC;), ANTIPHOSPHOLIPID SYNDROME; and in a variety of other diseases as well as in healthy individuals. In vitro, the antibody interferes with the conversion of prothrombin to thrombin and prolongs the partial thromboplastin time. In vivo, it exerts a procoagulant effect resulting in thrombosis mainly in the larger veins and arteries. It further causes obstetrical complications, including fetal death and spontaneous abortion, as well as a variety of hematologic and neurologic complications.
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.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES.
DNA present in neoplastic tissue.
Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.
Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.
Antibodies produced by a single clone of cells.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.
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.

Intracellular signalling: PDK1--a kinase at the hub of things. (1/12568)

Phosphoinositide-dependent kinase 1 (PDK1) is at the hub of many signalling pathways, activating PKB and PKC isoenzymes, as well as p70 S6 kinase and perhaps PKA. PDK1 action is determined by colocalization with substrate and by target site availability, features that may enable it to operate in both resting and stimulated cells.  (+info)

Myogenic signaling of phosphatidylinositol 3-kinase requires the serine-threonine kinase Akt/protein kinase B. (2/12568)

The oncogene p3k, coding for a constitutively active form of phosphatidylinositol 3-kinase (PI 3-kinase), strongly activates myogenic differentiation. Inhibition of endogenous PI 3-kinase activity with the specific inhibitor LY294002, or with dominant-negative mutants of PI 3-kinase, interferes with myotube formation and with the expression of muscle-specific proteins. Here we demonstrate that a downstream target of PI 3-kinase, serine-threonine kinase Akt, plays an important role in myogenic differentiation. Expression of constitutively active forms of Akt dramatically enhances myotube formation and expression of the muscle-specific proteins MyoD, creatine kinase, myosin heavy chain, and desmin. Transdominant negative forms of Akt inhibit myotube formation and the expression of muscle-specific proteins. The inhibition of myotube formation and the reduced expression of muscle-specific proteins caused by the PI 3-kinase inhibitor LY294002 are completely reversed by constitutively active forms of Akt. Wild-type cellular Akt effects a partial reversal of LY294002-induced inhibition of myogenic differentiation. This result suggests that Akt can substitute for PI 3-kinase in the stimulation of myogenesis; Akt may be an essential downstream component of PI 3-kinase-induced muscle differentiation.  (+info)

Regulation of G1 progression by the PTEN tumor suppressor protein is linked to inhibition of the phosphatidylinositol 3-kinase/Akt pathway. (3/12568)

PTEN/MMAC1 is a tumor suppressor gene located on chromosome 10q23. Inherited PTEN/MMAC1 mutations are associated with a cancer predisposition syndrome known as Cowden's disease. Somatic mutation of PTEN has been found in a number of malignancies, including glioblastoma, melanoma, and carcinoma of the prostate and endometrium. The protein product (PTEN) encodes a dual-specificity protein phosphatase and in addition can dephosphorylate certain lipid substrates. Herein, we show that PTEN protein induces a G1 block when reconstituted in PTEN-null cells. A PTEN mutant associated with Cowden's disease (PTEN;G129E) has protein phosphatase activity yet is defective in dephosphorylating inositol 1,3,4,5-tetrakisphosphate in vitro and fails to arrest cells in G1. These data suggest a link between induction of a cell-cycle block by PTEN and its ability to dephosphorylate, in vivo, phosphatidylinositol 3,4,5-trisphosphate. In keeping with this notion, PTEN can inhibit the phosphatidylinositol 3,4, 5-trisphosphate-dependent Akt kinase, a downstream target of phosphatidylinositol 3-kinase, and constitutively active, but not wild-type, Akt overrides a PTEN G1 arrest. Finally, tumor cells lacking PTEN contain high levels of activated Akt, suggesting that PTEN is necessary for the appropriate regulation of the phosphatidylinositol 3-kinase/Akt pathway.  (+info)

Akt-dependent potentiation of L channels by insulin-like growth factor-1 is required for neuronal survival. (4/12568)

The insulin-like growth factor-1 (IGF-1)/receptor tyrosine kinase recently has been shown to mediate neuronal survival and potentiate the activity of specific calcium channel subtypes; survival requires Akt, a serine/threonine kinase. We demonstrate here that Akt mediates the IGF-1-induced potentiation of L channel currents, but not that of N channels. Transient expression of wild-type, dominant-negative, and constitutively active forms of Akt in cerebellar granule neurons causes, respectively, no change in IGF-1/L channel potentiation, complete inhibition of potentiation, and a dramatic increase in basal L currents accompanied by the loss of ability to induce further increases. In no case is the IGF-1 potentiation of N currents affected. We additionally find that IGF-1 partially mediates granule neuron survival via L channel activity and that Akt-dependent L channel modulation is a necessary component. Interestingly, very brief exposure (1 min) to IGF-1 triggers nearly complete survival and requires L channel activity. These results strongly suggest that neuronal receptor tyrosine kinases can control long-term calcium-dependent processes via the rapid control of voltage-sensitive channels.  (+info)

Hyperglycemia inhibits insulin activation of Akt/protein kinase B but not phosphatidylinositol 3-kinase in rat skeletal muscle. (5/12568)

Sustained hyperglycemia impairs insulin-stimulated glucose utilization in the skeletal muscle of both humans and experimental animals--a phenomenon referred to clinically as glucose toxicity. To study how this occurs, a model was developed in which hyperglycemia produces insulin resistance in vitro. Rat extensor digitorum longus muscles were preincubated for 4 h in Krebs-Henseleit solution containing glucose or glucose + insulin at various concentrations, after which insulin action was studied. Preincubation with 25 mmol/l glucose + insulin (10 mU/ml) led to a 70% decrease in the ability of insulin (10 mU/ml) to stimulate glucose incorporation into glycogen and a 30% decrease in 2-deoxyglucose (2-DG) uptake, compared with muscles incubated with 0 mmol/l glucose. Glucose incorporation into lipid and its oxidation to CO2 were marginally diminished, if at all. The alterations of glycogen synthesis and 2-DG uptake were first evident after 1 h and were maximal after 2 h of preincubation; they were not observed in muscles preincubated with 25 mmol/l glucose + insulin for 5 min. Preincubation for 4 h with 25 mmol/l glucose in the absence of insulin produced a similar although somewhat smaller decrease in insulin-stimulated glycogen synthesis; however, it did not alter 2-DG uptake, glucose oxidation to CO2, or incorporation into lipids. Studies of insulin signaling in the latter muscles revealed that activation of Akt/protein kinase B (PKB) was diminished by 60%, compared with that of muscles preincubated in a glucose-free medium; whereas activation of phosphatidylinositol (PI) 3-kinase, an upstream regulator of Akt/PKB in the insulin-signaling cascade, and of mitogen-activated protein (MAP) kinase, a parallel signal, was unaffected. Immunoblots demonstrated that this was not due to a change in Akt/PKB abundance. The results indicate that hyperglycemia-induced insulin resistance can be studied in rat skeletal muscle in vitro. They suggest that impairment of insulin action in these muscles is related to inhibition of Akt/PKB by events that do not affect PI 3-kinase.  (+info)

Muscle fiber type-specific defects in insulin signal transduction to glucose transport in diabetic GK rats. (6/12568)

To determine whether defects in the insulin signal transduction pathway to glucose transport occur in a muscle fiber type-specific manner, post-receptor insulin-signaling events were assessed in oxidative (soleus) and glycolytic (extensor digitorum longus [EDL]) skeletal muscle from Wistar or diabetic GK rats. In soleus muscle from GK rats, maximal insulin-stimulated (120 nmol/l) glucose transport was significantly decreased, compared with that of Wistar rats. In EDL muscle from GK rats, maximal insulin-stimulated glucose transport was normal, while the submaximal response was reduced compared with that of Wistar rats. We next treated diabetic GK rats with phlorizin for 4 weeks to determine whether restoration of glycemia would lead to improved insulin signal transduction. Phlorizin treatment of GK rats resulted in full restoration of insulin-stimulated glucose transport in soleus and EDL muscle. In soleus muscle from GK rats, submaximal and maximal insulin-stimulated insulin receptor substrate (IRS)-1 tyrosine phosphorylation and IRS-1-associated phosphatidylinositol (PI) 3-kinase activity were markedly reduced, compared with that of Wistar rats, but only submaximal insulin-stimulated PI 3-kinase was restored after phlorizin treatment. In EDL muscle, insulin-stimulated IRS-1 tyrosine phosphorylation and IRS-1-associated PI-3 kinase were not altered between GK and Wistar rats. Maximal insulin-stimulated Akt (protein kinase B) kinase activity is decreased in soleus muscle from GK rats and restored upon normalization of glycemia (Krook et al., Diabetes 46:2100-2114, 1997). Here, we show that in EDL muscle from GK rats, maximal insulin-stimulated Akt kinase activity is also impaired and restored to Wistar rat levels after phlorizin treatment. In conclusion, functional defects in IRS-1 and PI 3-kinase in skeletal muscle from diabetic GK rats are fiber-type-specific, with alterations observed in oxidative, but not glycolytic, muscle. Furthermore, regardless of muscle fiber type, downstream steps to PI 3-kinase (i.e., Akt and glucose transport) are sensitive to changes in the level of glycemia.  (+info)

Protein kinase Czeta is a negative regulator of protein kinase B activity. (7/12568)

Protein kinase B (PKB), also known as Akt or RAC-PK, is a serine/threonine kinase that can be activated by growth factors via phosphatidylinositol 3-kinase. In this article we show that PKCzeta but not PKCalpha and PKCdelta can co-immunoprecipitate PKB from CHO cell lysates. Association of PKB with PKCzeta was also found in COS-1 cells transiently expressing PKB and PKCzeta, and moreover we found that this association is mediated by the AH domain of PKB. Stimulation of COS-1 cells with platelet-derived growth factor (PDGF) resulted in a decrease in the PKB-PKCzeta interaction. The use of kinase-inactive mutants of both kinases revealed that dissociation of the complex depends upon PKB activity. Analysis of the activities of the interacting kinases showed that PDGF-induced activation of PKCzeta was not affected by co-expression of PKB. However, both PDGF- and p110-CAAX-induced activation of PKB were significantly abolished in cells co-expressing PKCzeta. In contrast, co-expression of a kinase-dead PKCzeta mutant showed an increased induction of PKB activity upon PDGF treatment. Downstream signaling of PKB, such as the inhibition of glycogen synthase kinase-3, was also reduced by co-expression of PKCzeta. A clear inhibitory effect of PKCzeta was found on the constitutively active double PKB mutant (T308D/S473D). In summary, our results demonstrate that PKB interacts with PKCzeta in vivo and that PKCzeta acts as a negative regulator of PKB.  (+info)

A human protein kinase Bgamma with regulatory phosphorylation sites in the activation loop and in the C-terminal hydrophobic domain. (8/12568)

We have cloned human protein kinase Bgamma (PKBgamma) and found that it contains two regulatory phosphorylation sites, Thr305 and Ser472, which correspond to Thr308 and Ser473 of PKBalpha. Thus it differs significantly from the previously published rat PKBgamma. We have also isolated a similar clone from a mouse cDNA library. In human tissues, PKBgamma is widely expressed as two transcripts. A mutational analysis of the two regulatory sites of human PKBgamma showed that phosphorylation of both sites, occurring in a phosphoinositide 3-kinase-dependent manner, is required for full activity. Our results suggest that the two phosphorylation sites act in concert to produce full activation of PKBgamma, similar to PKBalpha. This contrasts with rat PKBgamma, which is thought to be regulated by 3-phosphoinositide-dependent protein kinase 1 alone.  (+info)

The serine/threonine kinase Akt (PKB/Rac) has been implicated as playing a role in the insulin-signaling pathway to glucose transport. Little is known regarding the regulation of Akt kinase activity in insulin-sensitive tissues, such as skeletal muscle, or whether this regulation is altered in insulin-resistant states such as NIDDM. We examined the effect of insulin on Akt kinase activity in skeletal muscle from six NIDDM patients and six healthy subjects. Whole-body insulin sensitivity, assessed by the euglycemic-hyperinsulinemic clamp, was significantly lower in NIDDM subjects (P , 0.001), and this was accompanied by impaired in vitro insulin-stimulated glucose transport in skeletal muscle. In both groups, insulin induced a significant increase in Akt kinase activity, but the response to maximal insulin (60 nmol/1) was markedly reduced in skeletal muscle from NIDDM subjects (66% of control levels, P , 0.01). Impaired Akt kinase activity was not accompanied by decreased protein expression of ...
Serine 1450 phosphorylation is critical for Akt-induced N-CoR misfolding.A, Serine to alanine substitution at 1450 abrogated Akt-induced N-CoR misfolding. Relat
Maintenance of skeletal muscle mass is dependent upon a balance between anabolic and catabolic processes and signaling through the Akt (protein kinase B, PKB)/mTOR (mammalian target of rapamycin) pathway is believed to influence protein synthesis as well as protein degradation in skeletal muscle [1 - 3]. The Akt family consists of three different isoforms, Akt1, Akt2 and Akt3 (PKBα, β, γ) encoded by separate genes [4]. Gene deletion studies have indicated a role for both Akt1 and Akt2 in growth and skeletal muscle size [5] and overexpression of Akt1 has been shown to result in skeletal muscle hypertrophy [6]. Akt activity is regulated by phosphorylation both at a threonine site (T308 for Akt1) located in the central catalytic domain (see e.g. [4,7]) and at a serine site (S473 for Akt1) located in the C-terminal hydrophobic regulatory domain (see e.g. [4,8]). Phosphorylations of both sites are believed to be necessary for full activation of Akt kinase activity [9] although this may not be true ...
TY - JOUR. T1 - High-Resolution Structure of the Pleckstrin Homology Domain of Protein Kinase B/Akt Bound to Phosphatidylinositol (3,4,5)-Trisphosphate. AU - Thomas, Christine C.. AU - Deak, Maria. AU - Alessi, Dario R.. AU - van Aalten, Daan M. F.. PY - 2002/7/23. Y1 - 2002/7/23. N2 - The products of PI 3-kinase activation, PtdIns(3,4,5)P3 and its immediate breakdown product PtdIns(3,4)P2, trigger physiological processes, by interacting with proteins possessing pleckstrin homology (PH) domains [1, 2]. One of the best characterized PtdIns(3,4,5)P3/PtdIns(3,4)P2 effector proteins is protein kinase B (PKB), also known as Akt [3-5]. PKB possesses a PH domain located at its N terminus, and this domain binds specifically to PtdIns(3,4,5)P3 and PtdIns(3,4)P2 with similar affinity [6, 7]. Following activation of PI 3-kinase, PKB is recruited to the plasma membrane by virtue of its interaction with PtdIns(3,4,5)P3/PtdIns(3,4)P2 [8-10]. PKB is then activated by the 3-phosphoinositide-dependent pro-tein ...
Service of the PI3K/AKT signal pathway is a known driving force for the progression to castration-recurrent prostate cancer (CR-CaP), which constitutes the major lethal phenotype of CaP. RUNX2 binding to the PIP promoter is increased in FOXO4-KD cells. Indeed, the forced expression of FOXO4 reversed the increased invasiveness of LNCaP/shFOXO4 Rabbit Polyclonal to DECR2 cells; the forced expression of FOXO4 did not alter RUNX2 protein levels, yet it decreased RUNX2 binding to the PIP promoter, resulting in PIP downregulation. Finally, there was a correlation between FOXO4, but not FOXO1 or FOXO3, downregulation and decreased metastasis-free survival in human CaP patients. Our data strongly recommend that improved PI3E/AKT-mediated metastatic invasiveness in Cover can be connected with FOXO4 reduction, and that systems to induce FOXO4 re-expression might suppress Cover metastatic aggressiveness. Intro Prostate tumor (Cover) continues to be the most diagnosed non-cutaneous tumor and the second ...
Aberration of receptor tyrosine kinases (RTKs), PTEN (phosphatase and tensin homolog deleted on chromosome 10), and PIK3CA (encodes the p110 subunit of phosphatidylinositol 3-kinase [PI3K]) frequently contribute to tumor progression through their ability to regulate the intracellular level of phosphatidylinositol-3,4,5- triphosphate (PIP3). PIP3 subsequently recruits 3-phosphoinositide- dependent kinase-1 (PDK-1), a serine/threonine kinase, to the plasma membrane and initiates PDK-1 kinase activity to phosphorylate AKT within the activation loop of the catalytic domain at the residue threonine-308 (T308). The mammalian target of rapamycin (mTOR) plays a critical role in the PI3K/AKT pathway. The mTOR kinase is present as two protein complexes, TORC1 and TORC2. The TORC1 complex is activated by PI3K/AKT and phosphorylates p70S6K and 4E-BP1 to modulate protein translation whereas the TORC2 complex phosphorylates AKT in the regulatory domain at residue serine 473 (S473). Phosphorylation of AKT at ...
The Akt/PKB kinase is a well-characterized effector of phosphoinositide 3-kinase (PI3K), and its deregulation plays important roles in the pathogenesis of human cancers. PI3K is necessary for the activation of Akt/PKB, and current models suggest that phosphatidylinositol-3,4,5-triphosphates produced upon growth factor stimulation recruit Akt/PKB to the plasma membrane by binding to its N-terminal pleckstrin homology (PH) domain. At the membrane, Akt/PKB is phosphorylated on two key residues: Thr308 (T308) of the activation loop by PDK1 (1, 2) and Ser473 (S473) in the hydrophobic motif of the C-terminal tail by a kinase whose identity has been elusive. The role of S473 phosphorylation is controversial, but there is an emerging view that it precedes the phosphorylation of T308 and is important for the recognition and activation of Akt/PKB by PDK1 (3-5).. The molecular identity of the S473 kinase (S473K), at times referred to as PDK2 or the hydrophobic motif (HM) kinase, has been hotly debated ...
The Akt (also referred to as protein kinase B) family of serine/threonine protein kinases is highly conserved in evolution.5 Akt1 and Akt2 share extensive sequence homology at the amino acid level, whereas Akt3 is slightly more divergent in structure and is expressed as a splice variant that lacks a regulatory phosphorylation site.6 Akt protein kinases are stimulated by a number of receptor tyrosine kinases, and this is mediated by the action of phosphatidylinositol 3-kinase (PI3K). PI3K phosphorylates inositol lipids that activate Akt directly by binding to its pleckstrin homology domain and promoting its translocation to the membrane and indirectly by activating the protein kinases that phosphorylate Akt. In the heart, Akt activation is regulated by insulin and nutritional status,7 exercise training,8-10 pressure overload,11 and advanced disease.12,13 In turn, Akt signaling regulates myocyte size, at least in part, through activation of mTOR-dependent progrowth pathways14,15 and suppression of ...
Akt-mediated phosphorylation of CDK2 regulates its dual role in cell cycle progression and apoptosis.: Here, we show that CDK2, an S-phase cyclin-dependent kina
Identified 2 decades ago, the serine/threonine kinase Akt has emerged as a promising target for drug development. Akt is critically involved in multiple signaling cascades, controlling cell growth and proliferation, and its activation is a prominent feature of many human cancers. On the basis of the strong rationale for targeting Akt for cancer therapy, multiple attempts to identify Akt inhibitors with acceptable pharmaceutical properties have been pursued (17). However, despite the significant progress in identifying Akt small-molecule inhibitors, selectivity has been a key issue for many previously reported ATP-competitive Akt inhibitors (relative to the kinome, especially within the AGC kinase family), raising concerns on safety and unclear mechanisms of action of these drugs. Even allosteric inhibitors, which held the promise of greater selectivity against the kinome, have been reported to exhibit unexpected nonkinase off-target effects (35).. GDC-0068 is a highly selective, orally available ...
Akt reportedly plays key roles in various cellular functions, including glucose transport, glycogen synthesis, DNA synthesis, antiapoptotic activity, and cell proliferation. Thus, the role of Akt is not limited to the metabolic actions of insulin, and intensive studies have focused on Akt in various fields of cell biology, tissue development, and so on. Several reports have described tissue-specific findings in mice transgenic for Akt. The heart (39-41) and pancreas (42,43), in which an active mutant of Akt was overexpressed, showed marked tissue enlargement. To study the role of hepatic Akt, constitutively active Akt was overexpressed selectively in the liver, and the resultant phenotype was investigated. We cannot rule out the possibility that myr-Akt stimulates some signals that endogenous Akt does not; however, because Akt is phosphorylated, translocated to the membrane fraction, and then transmits the signal(s), the overexpression of myr-Akt rather than wild-type Akt is more physiological, ...
Our data reveal a novel PS1 function by which this protein stimulates PI3K/Akt signaling and promotes cell survival. This conclusion is supported by the following observations: (1) absence of PS1 results in low levels of phosphorylated Akt and increased apoptosis; (2) exogenous PS1 stimulates Akt phosphorylation and rescues PS1 null cells from apoptosis; (3) a constitutively active PI3K restores Akt activation and suppresses apoptosis induced by the absence of PS1; (4) pharmacological inhibition of either PI3K or Akt prevents the PS1‐dependent Akt phosphorylation and caspase‐3 inactivation, indicating that the PI3K/Akt pathway mediates the anti‐apoptotic effects of PS1.. Cadherin-cadherin interactions initiate a cascade of signaling events that result in increased cadherin/PI3K association, activation of PI3K/Akt signaling and increased cell survival (Pece et al, 1999; Peluso et al, 2001; Kovacs et al, 2002; Tran et al, 2002; Yap and Kovacs, 2003). Our data that cadherin overexpression ...
The Alpha SureFire® Ultra™ HV Multiplex p-Akt 1/2/3 (Ser473) + Total Akt 1 assay kit is used to measure both the phosphorylation (Ser473) and total levels of endogenous Akt in cellular lysates. The kit measures phosphorylation on Ser473 of Akt 1/2/3, and total levels of Akt 1 only. The assay is an ideal system for the screening of modulators of receptor activation (e.g. agonists and antagonists) as well as agents acting intracellularly, such as small molecule inhibitors of signal transduction. The assay will measure Akt (Ser473) activation by either recombinant or endogenous receptors, and can be applied to primary cells.
Akt, or protein kinase B, is a multifunctional serine-threonine protein kinase implicated in a diverse range of cellular functions including cell metabolism, survival, migration, and gene expression. However, the in vivo roles and effectors of individual Akt isoforms in signaling are not explicitly clear. Here we show that the genetic loss of Akt1, but not Akt2, in mice results in defective ischemia and VEGF-induced angiogenesis as well as severe peripheral vascular disease. Akt1 knockout (Akt1-/-) mice also have reduced endothelial progenitor cell (EPC) mobilization in response to ischemia, and reintroduction of WT EPCs, but not EPCs isolated from Akt1-/- mice, into WT mice improves limb blood flow after ischemia. Mechanistically, the loss of Akt1 reduces the basal phosphorylation of several Akt substrates, the migration of fibroblasts and ECs, and NO release. Reconstitution of Akt1-/- ECs with Akt1 rescues the defects in substrate phosphorylation, cell migration, and NO release. Thus, the Akt1 ...
The serine/threonine kinase Akt, also known as protein kinase B (PKB), is a central node in cell signaling downstream of growth factors, cytokines, and other cellular stimuli. Aberrant loss or gain of Akt activation underlies the pathophysiological properties of a variety of complex diseases, includ …
1H10: High Resolution Structure of the Pleckstrin Homology Domain of Protein Kinase B/Akt Bound to Phosphatidylinositol (3,4,5)-Trisphosphate
Surucu B, et al. (2008) In vivo analysis of protein kinase B (PKB)/Akt regulation in DNA-PKcs-null mice reveals a role for PKB/Akt in DNA damage response and tumorigenesis. J Biol Chem 283, 30025-33 ...
These observations emphasize the sturdy association among the balance of Akt and mTORC1 routines and the development of steatosis. When Akt dominates above mTORC1, steatosis ensues, whilst when mTORC1 overshadows Akt, fat deposition is suppressed. Other designs of Akt suppression in the liver also result in a reduction in TG accumulation together with glucose intolerance equivalent to that of the Tsc12/two mice. Hence, inhibition of hepatic Akt action by any quantity of mechanisms leads to complete hepatic insulin resistance. On the opposite, growing Akt function in hepatocytes by immediate or oblique implies promotes lipogenesis and steatosis. These conclusions help our conclusion that the protecting result of mTORC1 from diet plan-induced steatosis is mediated by means of the inhibition of Akt signaling and underscore the prospective for focusing on Akt pharmacologically in the treatment method of steatosis. Rapamycin is frequently employed as an immunosuppressant adhering to renal transplant, ...
IC50: AKT1 32 nM, AKT2 17 nM, AKT3 47 nM, PKA 20 nMThe serine/threonine kinase AKT plays a pivotal role in signal transduction events involved in malignant transformation and chemoresistance and is an attractive target for the development of cancer therap
Some Akt inhibitors have produced functional cardiovascular effects such as marked hypotension that may limit their clinical benefit. There are no current data on whether this autonomic failure presents in humans at clinically used doses. We will test the hypothesis that Akt inhibition causes an acute decrease in sympathetic tone and lowers blood pressure ...
AKTRES is a biological substudy of the early effects and determinants of AKT inhibition using afuresertib in combination with chemotherapy in patients with
Related Articles Design, synthesis, in silico pharmacokinetics prediction and biological evaluation of 1,4-dihydroindeno[1,2-c]pyrazole chalcone as EGFR /Akt pathway inhibitors. Eur J Med Chem. 2018 Dec ...
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RAC-alpha serine/threonine-protein kinase is an enzyme that in humans is encoded by the AKT1 gene. This enzyme belongs to the AKT subfamily of serine/threonine kinases that contain SH2 (Src homology 2-like) domains. It is commonly referred to as PKB, or by both names as Akt/PKB ...
Haplotype: (AKT1_1251C,T) - ( AKT1_IVS14+32G,A) - ( AKT1_IVS14+66C,G) - ( AKT1_IVS14+93C,T) - ( AKT1_IVS+95-98delCTCA)(C-G-C-C-del), (AKT1_1251C,T) - ( AKT1_IVS14+32G,A) - ( AKT1_IVS14+66C,G) - ( AKT1_IVS14+93C,T) - ( AKT1_IVS14+98A,G)(C-G-C-C-A), (AKT1_1251C,T) - ( AKT1_IVS14+32G,A) - ( AKT1_IVS14+66C,G) - ( AKT1_IVS14+93C,T) - ( AKT1_IVS14+98A,G)(C-G-G-C-A), (AKT1_1251C,T) - ( AKT1_IVS14+32G,A) - ( AKT1_IVS14+66C,G) - ( AKT1_IVS14+93C,T) - ( AKT1_IVS14+98A,G) - ( AKT1_IVS14+105_106ins_CTCAC or CTCAG)(C-G-C-C-G-insCTCAG ...
AKT (phospho Ser473) antibody (AKT serine/threonine kinase 1) for ICC/IF, IHC-Fr, IHC-P, WB. Anti-AKT (phospho Ser473) pAb (GTX28932) is tested in Human, Mouse samples. 100% Ab-Assurance.
Phospho-AKT1 (Ser473), PE, clone: SDRNR, eBioscience™ 100 Tests; PE Phospho-AKT1 (Ser473), PE, clone: SDRNR, eBioscience™ Primary Antibodies Ad to Ak
The AKT family of serine threonine kinases is of critical importance with regard to growth factor signaling, cell proliferation, survival and oncogenesis. Engag
Akt1通过抑制凋亡过程从而参与细胞存活途径。Akt1亦能诱导蛋白合成通路,故其在导致骨骼肌肥大及的一般组织生长的细胞通路中是一种重要信号蛋白。因其可以阻断凋亡并继而促进细胞存活,现已表明Akt1在多种肿瘤中起到主要作用。Akt(先亦被称为Akt1)首先是在转化逆转录病毒AKT8中被鉴定为癌基因的[3]。 Akt2在胰岛素信号通路中是一重要的信号分子。需要其来诱导葡萄糖转运。在敲除Akt1但具正常Akt2的小鼠中,血糖稳态不受干扰,但动物体型会较小,这与Akt1在生长中起得作用是一致的。相反,Akt2缺失但具有正常Akt1的的小鼠生长略缺陷且表现出糖尿病表型(胰岛素抵抗),这从另一方面印证了Akt2对胰岛素受体信号通路更具特异性的这一设想[4]。 Akt3似乎主要在脑中表达,但其作用仍未明晰。有报道显示Akt3缺失的小鼠脑部较小[5]。 ...
Information and case study data for the PTMScan Direct PI3K / Akt Service offered by CST, which allows for targeted screening of 105 proteins within the Akt pathway.
Examination of the correlation between Akt Thr308 and Ser473 phosphorylation and the phosphorylation of Akt substrates. Triplicate samples of normal and patient
Akt-2 is a medicine available in a number of countries worldwide. A list of US medications equivalent to Akt-2 is available on the Drugs.com website.
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Growth factor receptor levels are aberrantly high in diverse cancers, driving the proliferation and survival of tumor cells. Understanding the molecular basis for this aberrant elevation has profound clinical implications. Here we show that the pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP) suppresses receptor tyrosine kinase (RTK) signaling output by a previously unidentified epigenetic mechanism unrelated to its previously described function as the hydrophobic motif phosphatase for the protein kinase AKT, protein kinase C, and S6 kinase. Specifically, we show that nuclear-localized PHLPP suppresses histone phosphorylation and acetylation, in turn suppressing the transcription of diverse growth factor receptors, including the EGF receptor. These data uncover a much broader role for PHLPP in regulation of growth factor signaling beyond its direct inactivation of AKT: By suppressing RTK levels, PHLPP dampens the downstream signaling output of two major oncogenic pathways, the
TY - JOUR. T1 - Polycystin-1 mitigates damage and regulates CTGF expression through AKT activation during cardiac ischemia/reperfusion. AU - Aránguiz, P.. AU - Romero, P.. AU - Vásquez, F.. AU - Flores-Vergara, R.. AU - Aravena, D.. AU - Sánchez, G.. AU - González, M.. AU - Olmedo, I.. AU - Pedrozo, Z.. PY - 2021/1/1. Y1 - 2021/1/1. N2 - During ischemia/reperfusion (I/R), cardiomyocytes activate pathways that regulate cell survival and death and release factors that modulate fibroblast-to-myofibroblast differentiation. The mechanisms underlying these effects are not fully understood. Polycystin-1 (PC1) is a mechanosensor crucial for cardiac function. This work aims to assess the role of PC1 in cardiomyocyte survival, its role in profibrotic factor expression in cardiomyocytes, and its paracrine effects on I/R-induced cardiac fibroblast function. In vivo and ex vivo I/R and simulated in vitro I/R (sI/R) were induced in wild-type and PC1-knockout (PC1 KO) mice and PC1-knockdown (siPC1) ...
Further evaluation of PI3K/AKT/mTOR pathway inhibitors is required to confirm whether the patterns of sensitivity observed in preclinical studies can be applied in the clinic. Although many early-phase trials have independently failed to identify a distinct association between clinical response and the most common alterations in the PI3K pathway (PIK3CA mutation and PTEN loss), a pooled analysis of 140 patients with various breast and gynecologic cancers treated with different PI3K/AKT/mTOR inhibitors identified an increased rate of RECIST-defined clinical responses among patients with PIK3CA mutations (75). A follow-up study pooling 1,012 patients with diverse cancers treated with PI3K/AKT/mTOR pathway inhibitors also identified an increased rate of response among tumors with PIK3CA H1047R mutation, but not those with other PIK3CA mutations or concurrent PIK3CA and KRAS mutations (76). The findings of these association studies have sparked interest in the research community; however, additional ...
The forkhead box O (FOXO) family of transcription factors regulates the expression of genes in cellular physiological events including apoptosis, cell-cycle control, glucose metabolism, oxidative stress resistance, and longevity. A central regulatory mechanism of FOXO proteins is phosphorylation by the serine-threonine kinase Akt/protein kinase B (Akt/PKB), downstream of phosphatidylinositol 3-kinase (PI3K), in response to insulin or several growth factors. Phosphorylation at three conserved residues results in the export of FOXO proteins from the nucleus to the cytoplasm, thereby decreasing expression of FOXO target genes. In contrast, the stress-activated c-Jun N-terminal kinase (JNK) and the energy sensing AMP-activated protein kinase (AMPK), upon oxidative and nutrient stress stimuli phosphorylate and activate FoxOs. Aside from PKB, JNK and AMPK, FOXOs are regulated by multiple players through several post-translational modifications, including phosphorylation, but also acetylation, ...
The forkhead box O (FOXO) family of transcription factors regulates the expression of genes in cellular physiological events including apoptosis, cell-cycle control, glucose metabolism, oxidative stress resistance, and longevity. A central regulatory mechanism of FOXO proteins is phosphorylation by the serine-threonine kinase Akt/protein kinase B (Akt/PKB), downstream of phosphatidylinositol 3-kinase (PI3K), in response to insulin or several growth factors. Phosphorylation at three conserved residues results in the export of FOXO proteins from the nucleus to the cytoplasm, thereby decreasing expression of FOXO target genes. In contrast, the stress-activated c-Jun N-terminal kinase (JNK) and the energy sensing AMP-activated protein kinase (AMPK), upon oxidative and nutrient stress stimuli phosphorylate and activate FoxOs. Aside from PKB, JNK and AMPK, FOXOs are regulated by multiple players through several post-translational modifications, including phosphorylation, but also acetylation, ...
Development of resistance to endocrine therapy is a clinical issue in estrogen receptor (ER)-positive breast cancer. Here we show that persistent activation of AKT/mTOR signaling is crucial to the acquisition of letrozole resistance in cell clones generated from MCF-7/AROM-1 aromatase-expressing breast cancer cells after prolonged letrozole exposure. ERα plays a marginal role in this context. As a proof of concept, the association between PI3K/AKT/mTOR signaling and insensitivity to endocrine therapies was confirmed in breast cancer patients who developed early letrozole resistance in neoadjuvant setting. In addition our results suggest that, regardless of the mechanism mediating the activation of AKT/mTOR pathway, either RAD001 or NVP-BEZ235 treatment may represent a promising strategy to overcome acquired resistance to letrozole in breast cancers dependent on AKT/mTOR signaling.
RAC Gamma Serine/Threonine Protein Kinase (Protein Kinase Akt 3 or Protein Kinase B Gamma or RAC PK Gamma or STK 2 or AKT3 or EC - Pipeline Review, H2 2017 Size and Share Published in 2017-08-29 Available for US$ 3500 at Researchmoz.us
3589 In women, endometrial cancer is the fourth in importance among all types of cancer. While most patients with disease recurrence after primary therapy are incurable, there is a subset of patients treated with surgery only who have recurrence confined to the pelvis that may be cured with appropriate radical pelvic irradiation. However, recurrent endometrial carcinoma, non-response to irradiation, age of the women or the presence of metastases are reasons that lead to the use chemotherapeutic agents. A major difficulty with chemotherapy is cellular resistance to chemotherapeutic drugs, and the mecanisms involved remain to be elucidated. Three isoforms of serine/threonine protein kinase Akt have been identified: Akt1, Akt2, Akt3, which are expressed and regulated differently in normal and cancer cells. The activity of Akt has been shown to suppress apoptosis and could be involved in chemoresistance. We have evaluated the role of Akt isoforms in chemoresistance of endometrial carcinoma cells, ...
In this study, we show that AKT overexpression alone in tamoxifen-sensitive, ER+ breast cancer cells is sufficient to confer tamoxifen-resistant cell proliferation. To identify genes that may be involved in AKT-induced tamoxifen resistance, we used microarray analysis to identify differentially expressed genes. Functional analysis revealed that two main biologic processes are altered: cell proliferation and cell motility (Supplementary Table S2), supporting our in vitro observations seen in AKT-expressing cells. Because expression of both AKT1 and AKT3 are significantly greater in patient breast tumors (Fig. 1) and because tumors exhibit greater cell proliferation and motility than normal cells, it was not surprising that these same differentially expressed genes also strongly correlated with breast carcinoma as compared with normal breast tissue in existing tumor cohorts, further validating our array data (Fig. 5B and Supplementary Fig. S4).. From our IPA analysis, estrogen and NFκB were ...
Accumulated evidence indicates that, by the phosphorylation of its physiological substrates, Akt promotes cell survival, proliferation and angiogenesis. While a number of Akt targets have been identified, the mechanism by which Akt regulates cell survival and growth and induces malignant transformation still remains elusive. During the last 5 years, I have shown that AKT1 cross-talks with Src/Stat3 pathway. AKT1 is a direct target gene of Stat3. Protein/mRNA levels and promoter activity of AKT1 are significantly induced by constitutively active Src and Stat3. Knockdown of Stat3 or dominant-negative Stat3 reduced AKT1 expression induced by constitutively active Src. Blockage of AKT1 expression largely reduced Stat3 function in cell survival and angiogenesis. Furthermore, I have shown that proapoptotic protein 24p3 is a major target of Akt to mediate IL3 signaling in hematopoietic cells. Forkhead transcription factor FOXO3a directly binds to and activates 24p3 promoter leading to expression of 24p3 in
TY - JOUR. T1 - Regulation of insulin action by ceramide. T2 - Dual mechanisms linking ceramide accumulation to the inhibition of Akt/protein kinase B. AU - Stratford, Suzanne. AU - Hoehn, Kyle L.. AU - Liu, Feng. AU - Summers, Scott A.. PY - 2004/8/27. Y1 - 2004/8/27. N2 - The sphingolipid ceramide negatively regulates insulin action by inhibiting Akt/protein kinase B (PKB), a serine/threonine kinase that is a central regulator of glucose uptake and anabolic metabolism. Despite considerable attention, the molecular mechanism accounting for this action of ceramide has remained both elusive and controversial. Herein we utilized deletion constructs encoding two different functional domains of Akt/PKB to identify which region of the enzyme conferred responsiveness to ceramide. Surprisingly the findings obtained with these separate domains reveal that ceramide blocks insulin stimulation of Akt/PKB by two independent mechanisms. First, using the isolated pleckstrin homology domain, we found that ...
PTEN/MMAC1 is a tumor suppressor gene that is mutated in a variety of cancers. PTEN encodes a phosphatase that recognizes phosphoprotein substrates and the phospholipid, phosphatidylinositol-3,4,5-triphosphate. PTEN inhibited cell growth and/or colony formation in all of the epithelial lines tested with one exception. The decrease in cellular proliferation was associated with an induction of apoptosis and an inhibition of signaling through the phosphatidylinositol 3′-kinase pathway. Akt/protein kinase B, a gene whose antiapoptotic function is regulated by phosphatidylinositol-3,4,5-triphosphate, was able to rescue cells from PTEN-dependent death. PTEN, therefore, appears to suppress tumor growth by regulating phosphatidylinositol 3′-kinase signaling. ...
TY - JOUR. T1 - Protein kinase B (c-Akt). T2 - A multifunctional mediator of phosphatidylinositol 3-kinase activation. AU - Coffer, Paul J.. AU - Jin, Jing. AU - Woodgett, James R.. PY - 1998/10/1. Y1 - 1998/10/1. N2 - While a plethora of extracellular molecules exist that modulate cellular functions via binding to membrane receptors inside the cell, their actions are mediated by relatively few signalling mechanisms. One of these is activation of phosphatidylinositol 3-kinase (PI-3K), which results in the generation of a membrane-restricted second messenger, polyphosphatidylinositides containing a 3-phosphate. How these molecules transduced the effects of agonists of PI-3K was unclear until the recent discovery that several protein kinases become activated upon exposure to 3-phosphorylated inositol lipids. These enzymes include protein kinase B (PKB)/AKT and PtdIns(3,4,5)P3-dependent kinases 1 and 2, the first two of which interact with 3-phosphorylated phosphoinositides via pleckstrin ...
Amplification or overexpression of HER-2/neu in cancer cells confers resistance to apoptosis and promotes cell growth. The cellular localization of p21Cip1/WAF1 has been proposed to be critical either in promoting cell survival or in inhibiting cell growth. Here we show that HER-2/neu-mediated cell growth requires the activation of Akt, which associates with p21Cip1/WAF1 and phosphorylates it at threonine 145, resulting in cytoplasmic localization of p21Cip1/WAF1. Furthermore, blocking the Akt pathway with a dominant-negative Akt mutant restores the nuclear localization and cell-growth-inhibiting activity of p21Cip1/WAF1. Our results indicate that HER-2/neu induces cytoplasmic localization of p21Cip1/WAF1 through activation of Akt to promote cell growth, which may have implications for the oncogenic activity of HER-2/neu and Akt.
Neuroblastoma is a paediatric cancer of the sympathetic nervous system. The single most important genetic indicator of poor clinical outcome is amplification of the MYCN transcription factor. One of many down-stream MYCN targets is miR-184, which is either directly or indirectly repressed by this transcription factor, possibly due to its pro-apoptotic effects when ectopically over-expressed in neuroblastoma cells. The purpose of this study was to elucidate the molecular mechanism by which miR-184 conveys pro-apoptotic effects. We demonstrate that the knock-down of endogenous miR-184 has the opposite effect of ectopic up-regulation, leading to enhanced neuroblastoma cell numbers. As a mechanism of how miR-184 causes apoptosis when over-expressed, and increased cell numbers when inhibited, we demonstrate direct targeting and degradation of AKT2, a major downstream effector of the phosphatidylinositol 3-kinase (PI3K) pathway, one of the most potent pro-survival pathways in cancer. The pro-apoptotic effects
Non-small cell lung cancers (NSCLC) are associated with constitutive activation of the phosphoinositide 3-kinase (PI3K) → Akt → mTOR pathway (1-3). The PI3K p85 regulatory subunit contains Src homology 2 (SH2) domains that interact with pYXXM sequences on activated receptor tyrosine kinases (RTK), such as the epidermal growth factor receptor (EGFR; ref 4). In turn, PI3K p85-mediated inhibition of the PI3K p110 catalytic subunit is relieved and p110 phosphorylates Akt (4). PI3K p110 also binds directly to Ras, linking PI3K signaling to the activation of Ras (5). Effective treatment of NSCLC with EGFR inhibitors is associated with suppression of PI3K activity and resistance to these inhibitors occurs with reactivation of the PI3K → Akt signaling pathway (4). The mTOR complex 1 (mTORC1) is a downstream effector of Akt, as well as other inputs, that regulates cell growth and is often dysregulated in human cancers (6). In this regard, agents that block the PI3K → Akt → mTOR pathway are ...
AKT (a serine/threonine protein kinase) has become a popular target for drug discovery campaigns, due to the fact that AKT inhibitors may help to treat a number of cancers. In this application note BioTek demonstrates an automated homogeneous assay to probe AKT phosphorylation at its serine 473 residue using endogenous levels of kinase expression within human primary HUVEC cells.
The observation of three distinct patterns (nuclear, cytoplasmic, and both) of localization of FKHR1 suggested the possibility that its intracellular localization might be regulated by extracellular growth signals or cell cycle progression. This hypothesis was tested by determining the localization of FKHR1-HA in serum-starved cells. CV1 cells transiently transfected with FKHR1-HA subsequently were maintained in serum-free medium for 24 hr before fixation. Under conditions of serum starvation FKHR1-HA was restricted to the nucleus in greater than 90% of the cells (Fig. 1 B and I). Moreover, treatment of serum-starved cells expressing FKHR1-HA with either 50 nM insulin-like growth factor I (Fig. 1O) or 10% serum (data not shown) for periods of time as short as 15-30 min was sufficient to cause export of FKHR1-HA from the nucleus in 70% of cells.. The growth factor stimulation of FKHR1-HA nuclear export could reflect either a passive process, such as inhibition of DNA binding leading to a ...
FSH stimulation of granulosa cells (GCs) results in increased hypoxia-inducible factor (HIF)-1alpha protein levels and HIF-1 activity that is necessary for up-regulation of certain FSH target genes including vascular endothelial growth factor. We report that the role of the phosphatidylinositol (PI)-3-kinase/AKT pathway in increasing HIF-1alpha protein in FSH-stimulated GCs extends beyond an increase in mammalian target of rapamycin-stimulated translation. FSH increases phosphorylation of the AKT target mouse double-minute 2 (MDM2); a phosphomimetic mutation of MDM2 is sufficient to induce HIF-1 activity. The PI3-kinase/AKT target forkhead box-containing protein O subfamily 1 (FOXO1) also effects the accumulation of HIF-1alpha as evidenced by the ability of a constitutively active FOXO1 mutant to inhibit the induction by FSH of HIF-1alpha protein and HIF-1 activity. Activation of the PI3-kinase/AKT pathway in GCs by IGF-I is sufficient to induce HIF-1alpha protein but surprisingly not HIF-1 activity.
AKT-mediated phosphorylation of ATG4B impairs mitochondrial activity and enhances the Warburg effect in hepatocellular carcinoma cells
12. Bergamot Polyphenolic Fraction Enhances Rosuvastatine-Induced Effect on LDL-Cholesterol, LOX-1 Expression and Protein Kinase B Phosphorylation in Patients with Hyperlipidemia: Gliozzi M1, Walker R, Muscoli S, Vitale C, Gratteri S, Carresi C, Musolino V, Russo V, Janda E, Ragusa S, Aloe A, Palma E, Muscoli C, Romeo F, Mollace V. This paper has been supported by PON a3_00359; PON03PE_00078_1 and PON03PE_00078_2 ...
rIPC [remote IPC (ischaemic preconditioning)] has been shown to invoke potent myocardial protection in animal studies and recent clinical trials. Although the important role of PI3K (phosphoinositide 3-kinase)/Akt activation in the cardioprotection afforded by local IPC is well described, our understanding of the intracellular signalling of rIPC remains incomplete. We therefore examined the hypothesis that the myocardial protection afforded by rIPC is mediated via the PI3K/Akt/GSK3β (glycogen synthase kinase 3β) signalling pathway, activation of which is associated with nuclear accumulation of β-catenin. rIPC was induced in mice using four cycles of 5 min of ischaemia and 5 min of reperfusion of the hindlimb using a torniquet. This led to reduced infarct size (19±4% in rIPC compared with 39±7% in sham; P,0.05), improved functional recovery and reduced apoptosis after global I/R (ischaemia/reperfusion) injury using a Langendorff-perfused mouse heart model. These effects were reversed by ...
FIGURE 3. The Keap1-independent regulation of Nrf2 protein stability. As illustrated, the Keap1-independent regulation of Nrf2 protein stability may occur via two pathways. One pathway is that GSK-3β phosphorylates Nrf2 enabling it to be recognized by β-TrCP and ubiquitylated by the β-TrCP-Cul1 E3 ubiquitin ligase complex for the eventual proteasomal degradation. The other pathway is dependent on Hrd1, an E3 ligase that ubiquitylates Nrf2 for proteasomal degradation. Hence, both pathways are negative regulators of Nrf2 protein stability, and inhibition of these pathways would cause Nrf2 activation and increased antioxidant gene expression. 2.3.1. β-TrCP-Cul1-Dependent Pathway Activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway causes Nrf2 activation, increasing ARE-driven antioxidant gene transcription [20]. A critical mediator in the PI3K/Akt-dependent pathway is glycogen synthase kinase-3beta (GSK-3β), which phosphorylates Nrf2 [21]. This phosphorylation enables Nrf2 to be ...
The phosphatidylinositol-3-kinase /protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway plays an important role in cell proliferation, growth, and angiogenesis.
As its role in tumor progression emerges, the PI3K/PKB (Akt) pathway presents an appealing cancer therapeutic target. Recent studies have investigated the mechanisms underlying the tumor-promoting effects of this pathway. PKB triggers a network that positively regulates G1/S cell cycle progression t …
Akt / ERK Inhibitor ONC201 in Treating Patients with Neuroendocrine Tumors That Are Locally Advanced, Metastatic, Recurrent, Refractory, or Cannot Be Removed by Surgery - NCT03034200
Principal Investigator:TODA Genji, Project Period (FY):2001 - 2002, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Circulatory organs internal medicine
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Alternative Name. AKT3; v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma); RAC-gamma serine/threonine-protein kinase; PKBG; PRKBG; RAC gamma; PKB gamma; RAC-gamma serine/threonine protein kinase; STK-2; PKB-GAMMA; RAC-gamma; RAC-PK-gamma. ...
14-3-3 theta/tau (Ser232), 14-3-3 zeta (Ser58), 14-3-3 zeta/delta (Thr232), AKT (Ser473), AKT (Thr308), AKT (Tyr326), AKT1 (Ser124), AKT1 (Ser246), AKT1 (Thr450), AKT1 (Thr72), AKT1 (Tyr474), AKT1S1 (Thr246), AKT2 (Ser474), BAD (Ser112), BAD (Ser134), BAD (Ser136), BAD (Ser155), BAD (Ser91/128), BCL-2 (Ser70), BCL-2 (Ser87), BCL-2 (Thr56), BCL-2 (Thr69), BIM (Ser69/65), Cyclin D1 (Thr286), eNOS (Ser1177), eNOS (Ser615), eNOS (Thr495), FAK (Ser910), FAK (Tyr397), FAK (Tyr407), FAK (Tyr576), FAK (Tyr861), FAK (Tyr925), FKHR (Ser256), FKHR (Ser319), FOXO1/3/4-PAN (Thr24/32), FOXO1A (Ser329), FOXO1A/3A (Ser322/325), Gab1 (Tyr627), Gab1 (Tyr659), Gab2 (Tyr643), GABA-RB (Ser434), GSK3a-b (Tyr216/279), GSK3a (Ser21), GSK3b (Ser9), IKKa (Thr23), IKKa/b (Ser180/181), IRS-1 (Ser1101), IRS-1 (Ser307), IRS-1 (Ser312), IRS-1 (Ser323), IRS-1 (Ser612), IRS-1 (Ser636), IRS-1 (Ser639), IRS-1 (Ser794), JAK1 (Tyr1022), LYN (Tyr507), mTOR (Ser2448), mTOR (Ser2481), mTOR (Thr2446), MYT1, p21Cip1 (Thr145), p27Kip1 ...
AKT3 - AKT3 (untagged)-Human v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma) (AKT3), transcript variant 1 available for purchase from OriGene - Your Gene Company.
2 3 4 eight 24 24C Hours soon after anti-CD3 Hours after anti-CD3 B Total Akt pAkt No anti-CD3 anti-CD3 No SPDB cost TU-100 Ginger GinsengJapanese Drug Pepper
USE OF ERBB4 AS A PROGNOSTIC AND THERAPEUTIC MARKER FOR MELANOMA - It is disclosed herein that members of the protein tyrosine kinase (PTK) family are highly mutated in patients with melanoma. Described herein are novel somatic mutations in the ERBB4 gene that result in increased kinase activity, transformation ability and anchorage-independent growth. These ERBB4 mutations contribute to the tumorogenicity of melanoma. Thus, provided herein is a method of predicting the prognosis of a patient with melanoma by detecting the presence or absence of a mutation in the ERBB4 gene. In some examples, the ERBB4 mutation is selected from G949A, G1354A, G1624A, C1630T, G1687A, G2506A and G2614A (numbering based on SEQ ID NO: 1). Also provided are methods of selecting a patient as a candidate for treatment with an ERBB4 and/or PI3K/AKT pathway inhibitor, and a method of identifying a therapeutic agent for the treatment of a subject diagnosed with melanoma. Oligonucleotides that specifically hybridize with ...
Introduction Weve shown previously that overexpression of constitutively dynamic Akt or activation of Akt due to constitutively dynamic Ras or individual epidermal development aspect receptor-2 (HER2) confers in breast cancers cells level of resistance to chemotherapy or radiotherapy. on phosphoinositide 3-kinase (PI3-K). An elevated baseline degree of Akt was within MCF7 cells treated with ionizing rays also. The cellular replies to doxorubicin-induced Akt phosphorylation had been potentiated following the appearance of Akt upstream activators including HER2, HER3 and focal adhesion kinase. Bottom line Used as well as our latest released outcomes displaying that constitutive Akt mediates level of resistance to radiotherapy or chemotherapy, our 443776-49-6 IC50 443776-49-6 IC50 present data claim that the doxorubicin-induced phosphorylation and activation of Akt might reveal a cellular protective mechanism of tumor cells to get over doxorubicin-induced cytotoxic results, which further works ...
AKT3 - AKT3 (untagged) - Homo sapiens v-akt murine thymoma viral oncogene homolog 3 (AKT3), transcript variant 3 available for purchase from OriGene - Your Gene Company.
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AKT1 overexpression lysate, 0.1 mg. Transient overexpression lysate of v-akt murine thymoma viral oncogene homolog 1 (AKT1), transcript variant 2
The multi-faceted roles of the PI3K-AKT pathway in melanoma. . 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.
Homo sapiens v-akt murine thymoma viral oncogene homolog 1 (AKT1), transcript variant 2, mRNA. (H00000207-R01V) - Products - Abnova
AKT (phospho Ser473) antibody (v-akt murine thymoma viral oncogene homolog 1) for IHC-P, IP, WB. Anti-AKT (phospho Ser473) pAb (GTX128414) is tested in Human, Mouse samples. 100% Ab-Assurance.
Akt (PKB, Rac kinase) is a 60kDa ser/thr kinase critical for controlling diverse cellular functions, including glucose metabolism, gene transcription, cell proliferation, and apoptosis. Akt phosphorylates a number of substrates including MBP, glycogen synthetase, PKA RII subunit, and histone H1. Akt is activated in res
... proto-oncogene proteins c-abl MeSH D12.776.624.664.700.168 - proto-oncogene proteins c-akt MeSH D12.776.624.664.700.169 - proto ... proto-oncogene proteins c-bcr MeSH D12.776.624.664.700.172 - proto-oncogene proteins c-cbl MeSH D12.776.624.664.700.174 - proto ... proto-oncogene proteins c-fes MeSH D12.776.624.664.700.179 - proto-oncogene proteins c-fos MeSH D12.776.624.664.700.180 - proto ... proto-oncogene proteins c-hck MeSH D12.776.624.664.700.182 - proto-oncogene proteins c-jun MeSH D12.776.624.664.700.183 - proto ...
... activating mutations in the proto-oncogene tyrosine-protein kinase Src, etc.) that lead to persistent activation of ERK and/or ... Ferrero M, Avivar A, García-Macías MC, Font de Mora J (July 2008). "Phosphoinositide 3-kinase/AKT signaling can promote AIB1 ... The nuclear receptor coactivator 3 also known as NCOA3 is a protein that, in humans, is encoded by the NCOA3 gene. NCOA3 is ... The ratio of PAX2 to AIB-1 protein expression may be predictive of the effectiveness of tamoxifen in breast cancer treatment. ...
Laine J, Künstle G, Obata T, Sha M, Noguchi M (2000). "The protooncogene TCL1 is an Akt kinase coactivator". Mol Cell. 6 (2): ... They are, T-cell leukemia/lymphoma protein 1A TCL1A encoded by oncogene TCL-1 SWISSPROT and Protein p13 MTCP-1 encoded by MTCP- ... In molecular biology, TCL-1/MTCP-1 is a protein domain found in proteins encoded for by two related protooncogenes, other words ... This protein exists as a homodimer. It interacts with AKT1, AKT2 and AKT3 via the PH protein domain. It interacts with PNPT1; ...
Src (gene) has been shown to interact with the following signaling pathways: PI3K Akt IKK NFkB Caspase 9 STAT3 p38 MAPK VEGF IL ... Proto-oncogene tyrosine-protein kinase Src, also known as proto-oncogene c-Src, or simply c-Src (cellular Src; pronounced "sarc ... Proto-oncogene tyrosine-protein kinase Src) at the PDBe-KB. Biology portal. ... This proto-oncogene may play a role in the regulation of embryonic development and cell growth. When src is activated, it ...
The mature form of the protein is a ligand for the product of the RET (rearranged during transfection) protooncogene. In ... GDNF has the ability to activate the ERK-1 and ERK-2 isoforms of MAP kinase in sympathetic neurons as well as P13K/AKT pathways ... Oncogene. 16 (5): 597-601. doi:10.1038/sj.onc.1201573. PMID 9482105. Amiel J, Salomon R, Attié T, Pelet A, Trang H, Mokhtari M ... GDNF is synthesized as a 211 amino acid-long protein precursor, pro-GDNF. The pre-sequence leads the protein to the endoplasmic ...
It found that upregulation of BZW2 promoted tumor growth and had a downstream upregulation effect on c-Myc, a proto-oncogene. A ... overexpression of BZW2 lead to overactivation of the AKT/mTOR signaling pathway by increasing phosphorylation of AKT and mTOR. ... "Protein BLAST: search protein databases using a protein query". blast.ncbi.nlm.nih.gov. Retrieved 2020-07-31. Koonin EV (August ... The coded protein is 419 amino acids long and weighs 48.3 kDa. As described in the name, the protein contains a leucine-zipper ...
Mdm2 is a proto-oncogene that directly antagonizes p53 to ubiquitination (Figure 1). The p53 protein is known as the "guardian ... The Akt/PKB signaling is a pathway that is pro-survival and growth. By activating Mdm2, the signal transduction pathway will ... The fusion protein AML1-ETO is commonly found in acute myeloid leukemia patients. p14ARF is a well known tumor suppressor that ... ETO is a protein with transcriptional repressing abilities located at the 8q22. Less than 1% of acute myeloid leukemia patients ...
... and the RET proto-oncogene. The active metabolite M4 has similar activity against ALK. Inhibition of ALK subsequently blocks ... Plasma protein binding of alectinib and M4 is over 99%. The enzyme mainly responsible for alectinib metabolism is CYP3A4; other ... cell signalling pathways, including STAT3 and the PI3K/AKT/mTOR pathway, and induces death (apoptosis) of tumour cells. When ... Interactions via other CYP enzymes and transporter proteins cannot be excluded but are unlikely to be of clinical significance ...
... is specific for the TK domain in abl (the Abelson proto-oncogene), c-kit and PDGF-R (platelet-derived growth factor ... The PI/PI3K/AKT/BCL-2 pathway is also affected. BCL-2 is responsible for keeping the mitochondria stable; this suppresses cell ... Imatinib is highly plasma protein-bound: dialysis is unlikely to be helpful removing imatinib. Its use is advised against in ... In vitro studies identified that a modified version of imatinib can bind to gamma-secretase activating protein (GSAP). GSAP ...
Proto-Oncogene+Proteins+c-sis at the US National Library of Medicine Medical Subject Headings (MeSH) McKinnon RD, Matsui T, ... Song G, Ouyang G, Bao S (2005). "The activation of Akt/PKB signaling pathway and cell survival". J. Cell. Mol. Med. 9 (1): 59- ... McClintock JT, Chan IJ, Thaker SR, Katial A, Taub FE, Aotaki-Keen AE, Hjelmeland LM (1992). "Detection of c-sis proto-oncogene ... The "c-Sis" oncogene is derived from PDGF. Age related downregulation of the PDGF receptor on islet beta cells has been ...
"The proto-oncogene p120(Cbl) is a downstream substrate of the Hck protein-tyrosine kinase". Biochem. Biophys. Res. Commun. 257 ... "FGFR2-Cbl interaction in lipid rafts triggers attenuation of PI3K/Akt signaling and osteoblast survival". Bone. 42 (6): 1032-9 ... "The adapter type protein CMS/CD2AP binds to the proto-oncogenic protein c-Cbl through a tyrosine phosphorylation-regulated Src ... "The protein product of the c-cbl protooncogene is the 120-kDa tyrosine-phosphorylated protein in Jurkat cells activated via the ...
ret+Proto-Oncogene+Proteins at the US National Library of Medicine Medical Subject Headings (MeSH) ... protein kinase activity. • kinase activity. • protein binding. • protein tyrosine kinase activity. • ATP binding. • Ras guanyl- ... "Characterization of the ret proto-oncogene products expressed in mouse L cells". Oncogene. 8 (11): 2925-2929. PMID 8414495.. ... "Characterization of RET proto-oncogene 3' splicing variants and polyadenylation sites: a novel C-terminus for RET". Oncogene. ...
More specifically, he focuses on "the roles of proto-oncogene proteins as elements of signal transduction pathways that control ... Regulation of neuronal survival by the Ser/Thr protein kinase Akt. Science 275:661-665. Erhardt, P., Tomaselli, K.J., and ... Identification of COUP-TF as a transcriptional repressor of the c-mos proto-oncogene. J. Biol. Chem. 274:36796-36800. Erhardt, ... Role of translation initiation factor 2B in control of cell survival by the phosphatidylinositol 3-kinase/Akt/glycogen synthase ...
This gene is a putative oncogene encoding a protein belonging to the AKT subfamily of serine/threonine kinases that contain SH2 ... Laine J, Künstle G, Obata T, Sha M, Noguchi M (August 2000). "The protooncogene TCL1 is an Akt kinase coactivator". Mol. Cell. ... The encoded protein is a general protein kinase capable of phosphorylating several known proteins. AKT2 has important roles in ... Laine J, Künstle G, Obata T, Sha M, Noguchi M (2000). "The protooncogene TCL1 is an Akt kinase coactivator". Mol. Cell. 6 (2): ...
Shigematsu H, Iwasaki H, Otsuka T, Ohno Y, Arima F, Niho Y (1997). "Role of the vav proto-oncogene product (Vav) in ... tyrosine kinase receptors and Src homology 3 domain proteins". Oncogene. 10 (8): 1475-83. PMID 7537362. Kapeller R, Toker A, ... Hellyer NJ, Kim MS, Koland JG (2001). "Heregulin-dependent activation of phosphoinositide 3-kinase and Akt via the ErbB2/ErbB3 ... Protein Pept. Sci. 5 (1): 1-8. doi:10.2174/1389203043486955. PMID 14965316. Joseph AM, Kumar M, Mitra D (2005). "Nef: " ...
Franke TF, Kaplan DR, Cantley LC, Toker A (January 1997). "Direct regulation of the Akt proto-oncogene product by ... Full activation of AKT occurs upon phosphorylation of serine 473 by the TORC2 complex of the mTOR protein kinase. The PI3K/AKT ... Many of these functions relate to the ability of class I PI3Ks to activate protein kinase B (PKB, aka Akt) as in the PI3K/AKT/ ... The interaction of activated PDK1 and AKT allows AKT to become phosphorylated by PDK1 on threonine 308, leading to partial ...
Proto-oncogene tyrosine-protein kinase Fyn (p59-FYN, Slk, Syn, MGC45350, Gene ID 2534) is an enzyme that in humans is encoded ... Yadav, Vipin; Denning, Mitchell F. (2011-05-01). "Fyn is induced by Ras/PI3K/Akt signaling and is required for enhanced ... By definition as a proto-oncogene, Fyn codes for proteins that help regulate cell growth. Changes in its DNA sequence transform ... SH3 domain-mediated protein-protein interaction blocking drug". Oncogene. 21 (13): 2037-50. doi:10.1038/sj.onc.1205271. PMID ...
SH3 domain-mediated protein-protein interaction blocking drug". Oncogene. 21 (13): 2037-50. doi:10.1038/sj.onc.1205271. PMID ... Beta-catenin is a proto-oncogene. Mutations of this gene are commonly found in a variety of cancers: in primary hepatocellular ... These changes were coordinate with Akt activation and glycogen synthase kinase 3β inhibition, suggesting once again that the ... DIX domains are unique: the only other proteins known to have a DIX domain are Dishevelled and DIXDC1. (The single Dsh protein ...
Proto-Oncogene+Proteins+c-met at the US National Library of Medicine Medical Subject Headings (MeSH) UniProtKB/Swiss-Prot entry ... PI3K activation also triggers a survival signal due to activation of the AKT pathway. The STAT pathway, together with the ... MET proto-oncogene (GeneID: 4233) has a total length of 125,982 bp, and it is located in the 7q31 locus of chromosome 7. MET is ... "Entrez Gene: MET met proto-oncogene (hepatocyte growth factor receptor)". Dean M, Park M, Le Beau MM, Robins TS, Diaz MO, ...
B-Raf proto-oncogene, casein kinase 2-interacting protein 1, and filamin A. Functions of PAK1 are regulated by its ability to ... Zhou GL, Zhuo Y, King CC, Fryer BH, Bokoch GM, Field J (November 2003). "Akt phosphorylation of serine 21 on Pak1 modulates Nck ... ARG-binding protein 2γ, hepatitis B virus X protein, STE20-related kinase adaptor protein α, RhoI, Klotho, N-acetylglucosaminyl ... These proteins serve as targets for the small GTP binding proteins Cdc42 and Rac and have been implicated in a wide range of ...
... as well as a number of proto-oncogenes (Raf, Myc, Myb, Rel, Src, Mos, ABL). The UPS is also involved in the regulation of ... To recognize protein as designated substrate, 19S complex has subunits that are capable to recognize proteins with a special ... These effects of siRNA-mediated PSMD2 inhibition were associated with changes in the balance between phosphorylated AKT and p38 ... Accordingly, misfolded proteins and damaged protein need to be continuously removed to recycle amino acids for new synthesis; ...
"PIKE-A is a proto-oncogene promoting cell growth, transformation and invasion". Oncogene. 26 (34): 4918-27. doi:10.1038/sj.onc. ... Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 is a protein that in humans is encoded by the AGAP2 gene. ... Knobbe CB, Trampe-Kieslich A, Reifenberger G (2005). "Genetic alteration and expression of the phosphoinositol-3-kinase/Akt ... Werden SJ, Barrett JW, Wang G, Stanford MM, McFadden G (2007). "M-T5, the ankyrin repeat, host range protein of myxoma virus, ...
... proto-oncogene". Oncogene. 7 (11): 2207-17. PMID 1279499.. *. Spritz RA, Droetto S, Fukushima Y (1992). „Deletion of the KIT ... Jahn T, Seipel P, Urschel S, Peschel C, Duyster J (2002). „Role for the adaptor protein Grb10 in the activation of Akt". Mol. ... 1991). „Expression of the YB5.B8 antigen (c-kit proto-oncogene product) in normal human bone marrow". Blood. 78 (1): 30-7. PMID ... 1992). „Steel factor stimulates the tyrosine phosphorylation of the proto-oncogene product, p95vav, in human hemopoietic cells ...
... "ets-2 is a target for an akt (Protein kinase B)/jun N-terminal kinase signaling pathway in macrophages of motheaten-viable ... "Characterization and localization of the products of the human homologs of the v-ets oncogene". Oncogene. 2 (2): 99-103. PMID ... "Regulation of transcription of the human presenilin-1 gene by ets transcription factors and the p53 protooncogene". The Journal ... Protein C-ETS2 is a protein that in humans is encoded by the ETS2 gene. The protein encoded by this gene belongs to the ETS ...
Proto-Oncogene+Proteins+c-akt at the US National Library of Medicine Medical Subject Headings (MeSH) Biology portal. ... Protein kinase B (PKB), also known as Akt, is a serine/threonine-specific protein kinase that plays a key role in multiple ... If Akt is not phosphorylated at this position, Akt does not fold in the right way. The T450-non-phosphorylated misfolded Akt is ... Akt can be O-GlcNAcylated by OGT. O-GlcNAcylation of Akt is associated with a decrease in T308 phosphorylation. Akt is normally ...
Crowder RJ, Freeman RS (Apr 1998). "Phosphatidylinositol 3-kinase and Akt protein kinase are necessary and sufficient for the ... "Tyrosine phosphorylation and tyrosine kinase activity of the trk proto-oncogene product induced by NGF". Nature. 350 (6314): ... Both Akt and RSK, components of the PI3K-Akt and MAPK pathways respectively, act to phosphorylate the cyclic AMP response ... The active Ras protein phosphorylates several proteins, along with the serine/threonine kinase, Raf. Raf in turn activates the ...
These data suggests that Shp2 may be a proto-oncogene. However, it has been reported that PTPN11/Shp2 can act as either tumor ... Akt PLCG2, PTK2B, Ras SLAMF1, SOCS3, SOS1, STAT3, STAT5A, and STAT5B. CagA is a protein and virulence factor inserted by ... "Induced direct binding of the adapter protein Nck to the GTPase-activating protein-associated protein p62 by epidermal growth ... PTPN11 is a protein tyrosine phosphatase (PTP) Shp2. PTPN11 is a member of the protein tyrosine phosphatase (PTP) family. PTPs ...
... behaves as an oncogene in cell systems and is an established protooncogene causally involved in the pathogenesis of ... and Fbxos containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by ... Akt activation by Skp2 is linked to aerobic glycolysis, as Skp2 deficiency impairs Akt activation, Glut1 expression, and ... The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), ...
Phospholipase C/PI3K/AKT, b) Ras subfamily/ERK, c) Protein kinase C, d) IP3-induced raising of cytosolic Ca2+, and e) Ca2+/ ... they are therefore classified as proto-oncogenes. FGFR1 is a member of the fibroblast growth factor receptor (FGFR) family, ... These proteins have continuously active FGFR1-derived tyrosine kinase and thereby continuously stimulated the cell growth and ... FGF-induced activation of FGFR1 also stimulates the activation of sprouty proteins SPRY1, SPRY2, SPRY3, and/or SPRY4 which in ...
Neoplasm: Tumor suppressor genes/proteins and Oncogenes/Proto-oncogenes. Ligand. Growth factors. ... protein binding. • cyclin-dependent protein serine/threonine kinase inhibitor activity. • ubiquitin protein ligase binding. • ... cyclin-dependent protein serine/threonine kinase activity. • protein kinase inhibitor activity. • protein kinase binding. • ... This article is about the p21Cip1 protein. For the p21/ras protein, see Ras (protein). For other uses, see P21 (disambiguation) ...
Franke TF, Kaplan DR, Cantley LC, Toker A (January 1997). "Direct regulation of the Akt proto-oncogene product by ... October 2004). "A rapid method for determining protein kinase phosphorylation specificity". Nat. Methods. 1 (1): 27-9. doi: ... TSC2 is a critical substrate of AKT,[17] and together with the laboratory of John Blenis they discovered that AKT ... They discovered that the Pleckstrin Homology domain of AKT binds to PtdIns(3,4,5)P3 (and PtdIns(3,4)P2) and that this binding ...
Neoplasm: Tumor suppressor genes/proteins and Oncogenes/Proto-oncogenes. Ligand. Growth factors. ... SH3 domain-mediated protein-protein interaction blocking drug". Oncogene. 21 (13): 2037-50. doi:10.1038/sj.onc.1205271. PMID ... protein binding. • ankyrin binding. • gamma-catenin binding. • beta-catenin binding. • GTPase activating protein binding. • ... Several proteins such as SNAI1/SNAIL,[58][59] ZFHX1B/SIP1,[60] SNAI2/SLUG,[61][62] TWIST1[63] and DeltaEF1[64] have been found ...
Mutations in the K-ras proto-oncogene are responsible for 10-30% of lung adenocarcinomas.[56][57] About 4% of non-small-cell ... This may occur through activation of signaling pathways such as Akt/GSK3Beta, MEK-ERK, Fas, and Par6.[61] ... Other immunotherapy treatments interfere with the binding of programmed cell death 1 (PD-1) protein with its ligand PD-1 ligand ... Similar to many other cancers, lung cancer is initiated by activation of oncogenes or inactivation of tumor suppressor genes.[ ...
Some genes are oncogenes: they are overexpressed in colorectal cancer. For example, genes encoding the proteins KRAS, RAF, and ... and activates the transcription of proto-oncogenes. These genes are normally important for stem cell renewal and ... The constitutive activation of PI3K/AKT/mTOR pathway may explain the loss of p27 and excess energy balance may up-regulate p27 ... which produces the APC protein. The APC protein prevents the accumulation of β-catenin protein. Without APC, β-catenin ...
MeSH(醫學主題詞)上面的Proto-Oncogene+Proteins+c-akt(美式英语) ... Akt,亦被称为蛋白激酶B(PKB),是在如葡萄糖代谢、凋亡、细胞增殖转录及细胞迁移等多种细胞过程中起到重要作用的一种丝氨酸/苏氨酸特异性蛋白激酶(英语:serine/threonine-specific protein kinase)。 ... Physiological functions of protein
Neoplasm: Tumor suppressor genes/proteins and Oncogenes/Proto-oncogenes. Ligand. Growth factors. ... protein binding. • enzyme binding. • metal ion binding. • identical protein binding. • ubiquitin protein ligase binding. • p53 ... protein ubiquitination. • negative regulation of protein processing. • establishment of protein localization. • response to ... protein deubiquitination. • protein sumoylation. • transcription factor catabolic process. • protein autoubiquitination. • ...
Neoplasm: Tumor suppressor genes/proteins and Oncogenes/Proto-oncogenes. Ligand. Growth factors. ... The gene that codes for the SDHB protein is nuclear, not mitchondrial DNA. However, the expressed protein is located in the ... "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).. *^ Sun, F; Huo, X; Zhai, Y; Wang, A; Xu, J; Su, D; Bartlam, M; Rao, Z ... Click on genes, proteins and metabolites below to link to respective articles. [§ 1] ...
... Proto-Oncogene Proteins at the US National Library of Medicine Medical Subject Headings (MeSH) ... Also, Less TOR, AKT, S6K and other changes in energy and metabolic pathways (such as AMPK, more oxygen consumption, more body ... MYC, MRTL, MYCC, bHLHe39, c-Myc, v-myc avian myelocytomatosis viral oncogene homolog, MYC proto-oncogene, bHLH transcription ... "The proto-oncogene c-myc in hematopoietic development and leukemogenesis". Oncogene. 21 (21): 3414-21. PMID 12032779. doi: ...
Mast/stem cell growth factor receptor (SCFR), aussi connue sous les noms de proto-oncogene c-Kit, tyrosine-protein kinase Kit ... Role for the adaptor protein Grb10 in the activation of Akt. », Mol. Cell. Biol., vol. 22, no 4,‎ février 2002. , p. 979-91 ( ... Organization and nucleotide sequence of the human KIT (mast/stem cell growth factor receptor) proto-oncogene. », Oncogene, vol. ... Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. », EMBO J., vol. 6, no 11 ...
Crowder RJ, Freeman RS (Apr 1998). "Phosphatidylinositol 3-kinase and Akt protein kinase are necessary and sufficient for the ... "Tyrosine phosphorylation and tyrosine kinase activity of the trk proto-oncogene product induced by NGF". Nature. 350 (6314): ... The active Ras protein phosphorylates several proteins, along with the serine/threonine kinase, Raf.[7] Raf in turn activates ... Both Akt and RSK, components of the PI3K-Akt and MAPK pathways respectively, act to phosphorylate the cyclic AMP response ...
Alexiadis V, Waldmann T, Andersen J, Mann M, Knippers R, Gruss C (2000). "The protein encoded by the proto-oncogene DEK changes ... Y14.The binding of these proteins to nuclear speckled domains has been measured recently and it may be regulated by PI3K/AKT/ ... These proteins are the most important components of the NMD mechanism. The EJC protein MAGOH, Y14 and eIF4AIII provide a ... EJC also interacts with a large number of additional proteins; most notably SR proteins. These interactions are suggested to be ...
1998). "The SH2-containing adapter protein GRB10 interacts with BCR-ABL". Oncogene. 17 (8): 941-8. doi:10.1038/sj.onc.1202024. ... "Role for the adaptor protein Grb10 in the activation of Akt". Mol. Cell. Biol. 22 (4): 979-91. doi:10.1128/MCB.22.4.979- ... and RET proto-oncogene. GRCh38: Ensembl release 89: ENSG00000106070 - Ensembl, May 2017 GRCm38: Ensembl release 89: ... Growth factor receptor-bound protein 10 also known as insulin receptor-binding protein Grb-IR is a protein that in humans is ...
In many types of cancers, the proto-oncogene c-Raf binds to the SARAH domain of MST2 and prevents RASSF1A-mediated MST2 ... and phosphorylation of the highly conserved Thr117 by Akt (protein kinase B), blocking autophosphorylation of Thr180, MST2 ... Serine/threonine-protein kinase 3 is an enzyme that in humans is encoded by the STK3 gene. Protein kinase activation is a ... "Role of the kinase MST2 in suppression of apoptosis by the proto-oncogene product Raf-1". Science. 306 (5705): 2267-70. doi: ...
When Wnt1 was discovered, it was first identified as a proto-oncogene in a mouse model for breast cancer. The fact that Wnt1 is ... Dsh proteins are present in all organisms and they all share the following highly conserved protein domains: an amino-terminal ... β-catenin may be directly phosphorylated at Ser552 by Akt, which causes its disassociation from cell-cell contacts and ... They identified a new mouse proto-oncogene that they named int1 (integration 1). Int1 is highly conserved across multiple ...
Calcium-Calmodulin-Dependent Protein Kinase Type 1 16% * Proto-Oncogene Proteins c-akt 16% ... Dive into the research topics of Substrate recognition by Ca,sup,2+,/sup,/calmodulin-dependent protein kinase kinase: Role of ... Substrate recognition by Ca2+/calmodulin-dependent protein kinase kinase: Role of the Arg-Pro-rich insert domain. ...
Proto-Oncogene Proteins c-akt 42% Powered by Pure, Scopus & Elsevier Fingerprint Engine™ © 2021 Elsevier B.V. ...
Proto-Oncogene Proteins c-akt 14% * Metabolic Networks and Pathways 12% 63 Downloads (Pure) ... PTEN protein phosphatase activity correlates with control of gene expression and invasion, a tumor-suppressing phenotype, but ... Suppression of cellular proliferation and invasion by the concerted lipid and protein phosphatase activities of PTEN. Davidson ... Oncogene. 29, 5, p. 687-697 11 p.. Research output: Contribution to journal › Article › peer-review ...
Proto-Oncogene Proteins c-akt Medicine & Life Sciences 18% * Morbidity Medicine & Life Sciences 18% ... phosphoinositide/protein kinase C, and mitogen-activated protein kinase/extracellular signal-regulated kinase cascades. ... phosphoinositide/protein kinase C, and mitogen-activated protein kinase/extracellular signal-regulated kinase cascades. ... phosphoinositide/protein kinase C, and mitogen-activated protein kinase/extracellular signal-regulated kinase cascades. ...
Rabbit Polyclonal AKT antibody [N3C2], Internal. Validated in WB, ICC/IF, IHC-P, IHC-Fr, IP, IHC. Tested in Human, Mouse, Rat, ... rac protein kinase alpha antibody , RAC-alpha serine/threonine-protein kinase antibody , proto-oncogene c-Akt antibody , RAC-PK ... AKT antibody recognizes AKT, a serine/threonine-specific protein kinase with a predicted molecular weight of ~57 kDa. AKT is a ... rac protein kinase beta antibody , RAC-beta serine/threonine-protein kinase antibody , v-akt murine thymoma viral oncogene ...
... physiology Phosphorylation Protein-Serine-Threonine Kinases/metabolism Proto-Oncogene Proteins/*metabolism Proto-Oncogene ... Spencer, J., Rice-Evans, C. and Williams, R.J. (2003) Modulation of pro-survival Akt/protein kinase B and ERK1/2 signaling ... Modulation of pro-survival Akt/protein kinase B and ERK1/2 signaling cascades by quercetin and its in vivo metabolites underlie ... physiology Mice Mitogen-Activated Protein Kinase 1/metabolism Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein ...
Protein Kinase C-alpha. *Protein Processing, Post-Translational. *Proto-Oncogene Proteins c-akt ...
Proto-Oncogene Proteins c-akt * Proteins - Proto-Oncogene Proteins c-akt * Proto-Oncogene Proteins - Proto-Oncogene Proteins c- ... Protein-Serine-Threonine Kinases * Protein-Serine-Threonine Kinases - ...
Cyr61 mediates hepatocyte growth factor-dependent tumor cell growth, migration, and Akt activation. ... Proto-Oncogene Proteins c-met * Subject Areas on Research. * A comparison of sunitinib with cabozantinib, crizotinib, and ... Activating mutation in MET oncogene in familial colorectal cancer. * Acute tissue injury activates satellite cells and promotes ... Inhibition of rhabdomyosarcoma cell and tumor growth by targeting specificity protein (Sp) transcription factors. ...
Q9P1W9: Serine/threonine-protein kinase pim-2. Protein function Proto-oncogene with serine/threonine kinase activity involved ... independent manner and in parallel to the PI3K-Akt pathway. Mediates survival signaling through phosphorylation of BAD, which ... The stabilization of MYC exerted by PIM2 might explain partly the strong synergism between these 2 oncogenes in tumorigenesis. ... Regulates cap-dependent protein translation in a mammalian target of rapamycin complex 1 (mTORC1)- ...
Missense Polypharmacy Population Groups Proto-Oncogene Proteins c-akt Receptors, G-Protein-Coupled Retrospective Studies ... Protein structure aids predicting functional perturbation of missense variants in and . Kroncke BM, Mendenhall J, Smith DK, ... Probing the mechanisms underlying modulation of quinidine sensitivity to cardiac I(Ks) block by protein kinase A-mediated I(Ks ...
Proto-Oncogene Proteins c-akt/*metabolism, Signal Transduction/*drug effects, Sucrose/*pharmacology, TOR Serine-Threonine ... Protein-Serine-Threonine Kinases/genetics/*metabolism, Proteins - Metabolism, Punicaceae/*chemistry, Signal Transduction - Drug ... Sucrose, But Not Glucose, Blocks IL1-beta-Induced Inflammatory Response in Human Chondrocytes by Inducing Autophagy via AKT/ ... DNA-Binding Proteins, Gene Expression, GENETIC aspects, Green Jonathan, Haqqi Tariq M, In Vivo Studies, Interleukins, June 2019 ...
FGR proto-oncogene, Src family tyrosine kinase. decreases activity. EXP. bosutinib results in decreased activity of FGR protein ... AKT serine/threonine kinase 1. decreases phosphorylation. decreases expression. ISO. bosutinib results in decreased ... LYN proto-oncogene, Src family tyrosine kinase. decreases activity. EXP. bosutinib results in decreased activity of LYN protein ... bosutinib inhibits the reaction [CTNNB1 protein binds to TCF4 protein]; bosutinib inhibits the reaction [SRC protein results in ...
Akt/protein kinase B (PKB) plays a critical role in the regulation of metabolism, transcription, cell migration, cell cycle ...
Myc Proto-Oncogene protein (MYC) * Ribosomal Protein S6 Kinase, 70kDa, Polypeptide 1 (RPS6KB1) ... V-Akt Murine Thymoma Viral Oncogene Homolog 1 (AKT1) * Interferon gamma (IFNG) ... synaptosomal-associated protein, 29kDa , synaptosomal-associated protein 29 , SNAP-29 , soluble 29 kDa NSF attachment protein ... Protein Überblick This gene, a member of the SNAP25 gene family, encodes a protein involved in multiple membrane trafficking ...
Proto-oncogene mutations( FOS), Myc proto-oncogene( MYC), transmembrane pyrimidine Bcl-2( BCL2). human minutes to hydration ... Non-protein DAMPs block ATP, undamped exon, photosynthesis proto and story. It is also architectural for the download ... heme of PI3K to RAD17 IL17 extrinsic authors in PI3K efficiency, cell of PIP3, and fusion of similar AKT polluting( Rodrigues ... Thr proteins converting of PKC proteins( Nishizuka 1995). chain serves transLife of PKC branches by signaling their end for ...
Functions of RAB proteins When activated receptors are internalized from the cell surface they are delivered to early endosomes ... RCP promotes recycling of EGFR1 in a manner that affects its signaling to PKB/AKT and MAPKs within endosomes (7). Since RCP ... The authors additional display that RCP could possibly be coprecipitated using the H-RAS protooncogene which RCP improved H-RAS ... exhibits TMC 278 the features of the oncogene Zhang et al. performed complete functional research to determine whether offers ...
Myc Proto-Oncogene protein (MYC) * Ribosomal Protein S6 Kinase, 70kDa, Polypeptide 1 (RPS6KB1) ... V-Akt Murine Thymoma Viral Oncogene Homolog 1 (AKT1) * Interferon gamma (IFNG) ... Protein Überblick The female gamete, the oocyte, serves the distinct purpose of transmitting the maternal genome and other ... oocyte-specific maternal effect factor , zygote arrest protein 1 , maternal factor , zygote arrest 1 , zygote arrest 1 variant ...
MET protooncogene, RTK) proto-oncogene family is found on the long arm of human chromosome 7, and the protein product is an RTK ... RON, MET, downstream pathway proteins including AKT and ERK1/2, and the phosphorylated proteins were detected using rabbit mAb ... Cross-talk between the proto-oncogenes Met and Ron. Oncogene. 2000;19:3041-9. ... Oncogene. 2000;19:5548-57. 4. Ronsin C, Muscatelli F, Mattei MG, Breathnach R. A novel putative receptor protein tyrosine ...
FuransGinkgolidesNeuroprotective AgentsPC12 CellsProto-Oncogene ProteinsProto-Oncogene Proteins c-bcl-2Proto-Oncogene Proteins ... Bilobalide prevents apoptosis through activation of the PI3K/Akt pathway in SH-SY5Y cells. ... MessengerRatsReactive Oxygen SpeciesTumor Suppressor Protein p53bcl-2-Associated X Proteinbcl-X Protein ... Proto-Oncogene Proteins. *Proto-Oncogene Proteins c-bcl-2. *Proto-Oncogene Proteins c-myc ...
ReticulumEpithelial CellsJNK Mitogen-Activated Protein KinasesLungMitochondriaPhosphorylationProto-Oncogene Proteins c-bcl-2 ... Indomethacin induces apoptosis in 786-O renal cell carcinoma cells by activating mitogen-activated protein kinases and AKT. ... PDTC/Cu complex dramatically enhanced the JNK protein phosphorylation and ERK protein phosphorylation proteins. PDTC/Cu complex ... PDTC/Cu complex dramatically enhanced the JNK protein phosphorylation and ERK protein phosphorylation proteins. PDTC/Cu complex ...
lymphocyte-specific protein tyrosine kinase. 0.998. SRC. v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian). ... met proto-oncogene (hepatocyte growth factor receptor). 0.028. Human HLA-DMB. major histocompatibility complex, class II, DM ... v-akt murine thymoma viral oncogene homolog 1. 0.024. CIITA. class II, major histocompatibility complex, transactivator. 0.024 ... lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa). 0.282. ...
BRCA1 interacting protein C-terminal helicase 1 / Fanconi anemia group J protein ... BRCA1 interacting protein C-terminal helicase 1 / Fanconi anemia group J protein ... BRCA1 interacting protein C-terminal helicase 1 / Fanconi anemia group J protein ...
... inhibitors have been advanced to investigational clinical trials in patients with activating mutations in B-Raf proto-oncogene ... The Src homology region 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2) is a key regulator of MAPK pathway downstream ... Aberrant activation of the mitogen-activated protein kinase pathway frequently drives tumor growth, and the ERK1/2 kinases are ... ASTX029 Extracellular Signal-Related Protein Kinases (ERK 1/2) Inhibitor (Solid Tumors) ...
Myc Proto-Oncogene protein (MYC) * Ribosomal Protein S6 Kinase, 70kDa, Polypeptide 1 (RPS6KB1) ... V-Akt Murine Thymoma Viral Oncogene Homolog 1 (AKT1) * Interferon gamma (IFNG) ... anti-Regulatory Solute Carrier Protein, Family 1, Member 1 Anticorps * anti-Related RAS Viral (R-Ras) Oncogene Homolog 2 ... Target Regulator of G-Protein Signalling 12 (RGS12) * Regulator of G-Protein Signalling 12 (RGS12) ...
Myc Proto-Oncogene protein (MYC) * Ribosomal Protein S6 Kinase, 70kDa, Polypeptide 1 (RPS6KB1) ... V-Akt Murine Thymoma Viral Oncogene Homolog 1 (AKT1) * Interferon gamma (IFNG) ... Protein level used designations for ABCA9 ATP-binding cassette, sub-family A (ABC1), member 9 , ATP-binding cassette sub-family ... ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct ...
G-quadruplex formation within the promoter of the KRAS proto-oncogene and its effect on transcription. Nucleic Acids Res 2006; ... Role of protein kinase Cζ in Ras-mediated transcriptional activation of vascular permeability factor/vascular endothelial ... Inhibition of Akt inhibits growth of glioblastoma and glioblastoma stem-like cells ... Single-molecule conformational analysis of G-quadruplex formation in the promoter DNA duplex of the proto-oncogene c-kit. J Am ...
Myc Proto-Oncogene protein (MYC) * Ribosomal Protein S6 Kinase, 70kDa, Polypeptide 1 (RPS6KB1) ... V-Akt Murine Thymoma Viral Oncogene Homolog 1 (AKT1) * Interferon gamma (IFNG) ... Protein level used designations for DNAH8 axonemal beta dynein heavy chain 8 , ciliary dynein heavy chain 8 , dynein heavy ... The protein encoded by this gene is a heavy chain of an axonemal dynein involved in sperm and respiratory cilia motility. ...
Myc Proto-Oncogene protein (MYC) * CD5 * Ribosomal Protein S6 Kinase, 70kDa, Polypeptide 1 (RPS6KB1) ... V-Akt Murine Thymoma Viral Oncogene Homolog 1 (AKT1) * Interferon gamma (IFNG) ... anti-Transmembrane Protein, Adipocyte Asscociated 1 Anticorps * anti-Transmembrane Protein with EGF-Like and Two Follistatin- ... Protein level used designations for TFF3 trefoil factor 3 (intestinal) , intestinal trefoil factor , trefoil factor 3 , ...
Myc Proto-Oncogene protein (MYC) * Ribosomal Protein S6 Kinase, 70kDa, Polypeptide 1 (RPS6KB1) ... V-Akt Murine Thymoma Viral Oncogene Homolog 1 (AKT1) * Interferon gamma (IFNG) ... Protein level used designations for IFI16 gamma-interferon-inducible protein 16 , interferon-gamma induced protein IFI 16 , ... The encoded protein contains domains involved in DNA binding, transcriptional regulation, and protein-protein interactions. The ...
  • The serine-threonine protein kinase encoded by the AKT1 gene is catalytically inactive in serum-starved primary and immortalized fibroblasts. (genetex.com)
  • Quercetin induced potent inhibition of both Akt/PKB and ERK phosphorylation, resulting in reduced phosphorylation of BAD and a strong activation of caspase-3. (reading.ac.uk)
  • 10 microM) the inhibition of Akt phosphorylation was transient and eventually returned to basal levels. (reading.ac.uk)
  • Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression, the regulation of cap-dependent protein translation and through survival signaling by phosphorylation of a pro-apoptotic protein, BAD. (scbdd.com)
  • Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase transcriptional activity. (scbdd.com)
  • Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. (scbdd.com)
  • PDTC/Cu complex dramatically enhanced the JNK protein phosphorylation and ERK protein phosphorylation proteins. (unboundmedicine.com)
  • PDTC/Cu complex did not affect the p38 protein phosphorylation. (unboundmedicine.com)
  • The possible cardioprotective actions of lithium may involve an extensive range of signaling pathways, including the Wnt/glycogen synthase kinase-3β phosphatidylinositol-3-kinase/protein kinase B, phosphoinositide/protein kinase C, and mitogen-activated protein kinase/extracellular signal-regulated kinase cascades. (elsevier.com)
  • Much recent interest has focused on the potential of flavonoids to interact with intracellular signaling pathways such as with the mitogen-activated protein kinase cascade. (reading.ac.uk)
  • We have investigated whether the observed strong neurotoxic potential of quercetin in primary cortical neurons may occur via specific and sensitive interactions within neuronal mitogen-activated protein kinase and Akt/protein kinase B (PKB) signaling cascades, both implicated in neuronal apoptosis. (reading.ac.uk)
  • Aberrant activation of the mitogen-activated protein kinase pathway frequently drives tumor growth, and the ERK1/2 kinases are positioned at a key node in this pathway, making them important targets for therapeutic intervention. (astx.com)
  • Nevertheless mutations in TMC 278 RABs and their BMPR2 binding protein never have been identified in a significant proportion of cancers. (opt-inviral.com)
  • Recently, a number of ERK1/2 inhibitors have been advanced to investigational clinical trials in patients with activating mutations in B-Raf proto-oncogene or Ras. (astx.com)
  • VEGF expression is known to be induced by a variety of factors, including hypoxia, pH, activated oncogenes, inactivated tumor suppressor genes, and growth factors (reviewed in ref. 21 ). (aacrjournals.org)
  • B) An evaluation of pro- and anti-apoptotic proteins appearance in untreated WSU-FSCCL (FS) and FC-TxFL2 (FC) cell lines. (alexjordan.org)
  • Together these data suggest that quercetin and to a lesser extent its O-methylated metabolites may induce neuronal death via a mechanism involving an inhibition of neuronal survival signaling through the inhibition of both Akt/PKB and ERK rather than by an activation of the c-Jun N-terminal kinase-mediated death pathway. (reading.ac.uk)
  • Regulates cap-dependent protein translation in a mammalian target of rapamycin complex 1 (mTORC1)-independent manner and in parallel to the PI3K-Akt pathway. (scbdd.com)
  • 2015) and nuclear triskelion pathway proteins, opposite as EGFR( Kamalati et al. (evakoch.com)
  • To conclude, venetoclax induced a discharge of BIM protein from BCL-2 that connected with activation from the intrinsic apoptotic pathway. (alexjordan.org)
  • Responding to many extracellular stimuli, AKT is active through major signaling nodes that include GSK3, FOXO, and TSC2/mTORC1. (genetex.com)
  • The procedure induced an activation of caspase-3 also, JNK1/2 and a cleavage of Bet protein. (alexjordan.org)
  • Recombinant protein encompassing a sequence within the center region of human Akt1/2/3. (genetex.com)
  • Immunoprecipitation of Akt1/2/3 protein from 293T whole cell extracts using 5 μg of Akt1/2/3 antibody [N3C2], Internal (GTX121937). (genetex.com)
  • Dosage-dependent effects of Akt1/protein kinase Balpha (PKBalpha) and Akt3/PKBgamma on thymus, skin, and cardiovascular and nervous system development in mice. (unil.ch)
  • Disruption of BCL-2/BIM complicated and activation of caspase-dependent apoptosis To help expand study the function of BIM protein in venetoclax-induced apoptosis, immunoprecipitation (IP-WB) using BIM antibody was utilized. (alexjordan.org)
  • Open up in another window Body 3 Cellular occasions proceeding and associated venetoclax induced apoptosis in FC-TxFL2 cell range(A) BIM protein immunoprecipitation accompanied by BCL-2, MCL-1 and BCL-XL WB recognition of lysates of FC-TxFL2 cells treated with 100 nM venetoclax for 2 H. (WL C entire cell lysate) (B) Loss of mitochondrial potential after 1 H venetoclax treatment examined by JC-1 assay. (alexjordan.org)
  • Spectraplakins are giant cytolinkers, which have the rare ability to bind to all three main cytoskeletal elements and with transmembrane proteins to coordinate cytoskeletal dynamics. (cenicriviroc.info)
  • Functions of RAB proteins When activated receptors are internalized from the cell surface they are delivered to early endosomes where key decisions are made as to whether receptors are sent to late endosomes for. (opt-inviral.com)
  • In the developing nervous system AKT is a critical mediator of growth factor-induced neuronal survival. (genetex.com)
  • Lower levels of quercetin also induced strong activation of the pro-survival transcription factor cAMP-responsive element-binding protein, although this did not prevent neuronal damage. (reading.ac.uk)
  • AKT is a family of three highly homologous isoforms that have more than a hundred substrates, with most of these regulated by all three proteins. (genetex.com)
  • RCP promotes recycling of EGFR1 in a manner that affects its signaling to PKB/AKT and MAPKs within endosomes (7). (opt-inviral.com)
  • MCF10A cells with conditional induction from the Src proto-oncogene, they could function as the predominant Dystonin tumour suppressor variants in breast epithelial cells. (cenicriviroc.info)
  • The Bcl-2 mRNA and protein expressions were decreased in lung epithelial cells treated with PDTC/Cu complex, which could be reversed by SP600125. (unboundmedicine.com)
  • E) An evaluation of BCL-2, MCL-1, BIM, and cleaved caspase-3 protein expressions in major FL examples. (alexjordan.org)
  • growth between other cells in the repair of nucleus of result collagen TP53-regulated damage protein. (evakoch.com)
  • Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation. (scbdd.com)
  • The authors additional display that RCP could possibly be coprecipitated using the H-RAS protooncogene which RCP improved H-RAS activity and markedly improved activation from the downstream focus on MAPK recommending a potential system of actions for the oncogenic aftereffect of RCP (1). (opt-inviral.com)
  • Intriguingly the p85 subunit of the PI3K complex that acts as a RAB GTPase-activating protein albeit with weak activity toward RAB11 (9) is mutated in a significant number of gliomas and rarely in other cancer lineages. (opt-inviral.com)
  • Non-transfected (-) and transfected (+) 293T whole cell extracts (30 μg) were separated by 10% SDS-PAGE, and the membrane was blotted with AKT antibody [N3C2], Internal (GTX121937) diluted at 1:1000. (genetex.com)
  • Strikingly these ramifications of RCP were specific for H-RAS with limited effects for the N-RAS or K-RAS protooncogenes. (opt-inviral.com)
  • O-Methylated quercetin metabolites inhibited Akt/PKB to lesser extent and did not induce such strong activation of caspase-3, which was reflected in the lower amount of damage they inflicted on neurons. (reading.ac.uk)
  • The stabilization of MYC exerted by PIM2 might explain partly the strong synergism between these 2 oncogenes in tumorigenesis. (scbdd.com)
  • Six waves of VEGF-A download transplant production systems proceedings of the international symposium on transplant, building 121, 145, 165, 183, 189, and 206 polyA level principles, and two sphingolipids of VEGF-B( 167 and 186 proteins) encode activated by often aligned levels. (evakoch.com)
  • AKT antibody recognizes AKT, a serine/threonine-specific protein kinase with a predicted molecular weight of ~57 kDa. (genetex.com)

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