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
Akt/protein kinase B (PKB) plays a critical role in the regulation of metabolism, transcription, cell migration, cell cycle progression, and cell survival. The existence of viable knockout mice for each of the three isoforms suggests functional redundancy. We generated mice with combined mutant alleles of Akt1 and Akt3 to study their effects on mouse development. Here we show that Akt1-/- Akt3+/- mice display multiple defects in the thymus, heart, and skin and die within several days after birth, while Akt1+/- Akt3-/- mice survive normally. Double knockout (Akt1-/-) Akt3-/-) causes embryonic lethality at around embryonic days 11 and 12, with more severe developmental defects in the cardiovascular and nervous systems. Increased apoptosis was found in the developing brain of double mutant embryos. These data indicate that the Akt1 gene is more essential than Akt3 for embryonic development and survival but that both are required for embryo development. Our results indicate isoform-specifi
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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Indy Academy Membership and Services. Chris Clemens is an Indianapolis native and founded the Indianapolis Golf Academy at Winding River in 2013. Chris is a PGA member with 20 years of teaching experience. An accomplished player with numerous amateur, collegiate and professional victories. I love to change kids lives and offer a Complete Training Process. I enjoy teaching people to have fun with the game of golf. I believe in being a mentor coach who can teach all levels and offer a place where golfers can find everything they need in a coaching experience.. Certification\Training:. -NCAA Coach -K-Coach 3D Human Motion Certified Instructor Level 2. -Certified Titleist Club Fitter. -American Development Model Certification. -Certified Club Performance and Fitting Specialist-Mitchell Golf. -Fitness Evaluation & Training Experience. -Physical Therapy Training. -Child Abuse Prevention Certification. -Club Repair Training. -Certified SeeMore Putter Fitter. -Nike Certified Fitter ...
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. ...
... the BRAF and ROS1 genes code for serine/threonine-protein kinase B-Raf and proto-oncogene tyrosine-protein kinase, respectively ... and RET proto-oncogene receptor, respectively, all of which activate the PI3K/AKT/mTOR pathway; 2) ... Excessive activation of the PI3K/AKT/mTOR pathway is known to promote the development of various tumor types and may be ... "RBM27 RNA binding motif protein 27 [Homo sapiens (Human)] - Gene - NCBI". "TPR translocated promoter region, nuclear basket ...
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. Portal: Biology (Articles with short description, Short description ... 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 ... it is received by RET proto-oncogene (RET) and by forming gradient with SCF it divides the spermatogonia into two cells. As the ... 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 ... 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 ... The decrease of AML1-ETO also results in lower levels of C-KIT kinases, Akt/PKB, STAT3, and Erk1/2 - all of which are involved ...
... 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 ...
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): ...
Jahn T, Seipel P, Urschel S, Peschel C, Duyster J (February 2002). "Role for the adaptor protein Grb10 in the activation of Akt ... 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 ... 1998). "The SH2-containing adapter protein GRB10 interacts with BCR-ABL". Oncogene. 17 (8): 941-8. doi:10.1038/sj.onc.1202024. ...
... and D-L1 proteins, expression of the MYC, BCL2, MYD88nd, and CREBBP genes, and expression of the PI3K/AKT/mTOR, JAK-STAT, B- ... MYC: This protooncogene's product, Myc, encodes a transcription factor which regulates the expression of other genes whose ... February 2020). "Potent efficacy of MCL-1 inhibitor-based therapies in preclinical models of mantle cell lymphoma". Oncogene. ... Its product, Bcl-2 protein, regulates cellular apoptosis (i.e. survival) by inhibiting the apoptosis-causing proteins, Bcl-2- ...
Proto-Oncogene+Proteins+c-akt at the US National Library of Medicine Medical Subject Headings (MeSH) Portal: Biology (Articles ... Akt1 is involved in the PI3K/AKT/mTOR pathway and other signaling pathways.[citation needed] The Akt proteins possess a protein ... Tumor cells that have constantly active Akt may depend on Akt for survival. Therefore, understanding the Akt proteins and their ... Protein kinase B (PKB), also known as Akt, is the collective name of a set of three serine/threonine-specific protein kinases ...
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 ...
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/ ... It has been shown that malignant B cells maintain a "tonic" activity of PI3K/Akt axis via upregulation of an adaptor protein ...
SH3 domain-mediated protein-protein interaction blocking drug". Oncogene. 21 (13): 2037-2050. 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 ...
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: " ...
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, ...
Aoki M, Hamada F, Sugimoto T, Sumida S, Akiyama T, Toyoshima K (Oct 1993). "The human cot proto-oncogene encodes two protein ... Kane LP, Mollenauer MN, Xu Z, Turck CW, Weiss A (Aug 2002). "Akt-dependent phosphorylation specifically regulates Cot induction ... "Identification and characterization of protein products of the cot oncogene with serine kinase activity". Oncogene. 6 (9): 1515 ... Lin X, Cunningham ET, Mu Y, Geleziunas R, Greene WC (Feb 1999). "The proto-oncogene Cot kinase participates in CD3/CD28 ...
... which is a proto-oncogene associated with breast, testicular germ cell, gastric, and esophageal tumours. HER2 proteins have ... Signaling pathways activated by HER2 include: mitogen-activated protein kinase (MAPK) phosphoinositide 3-kinase (PI3K/Akt) ... ERBB2, a known proto-oncogene, is located at the long arm of human chromosome 17 (17q12). The ErbB family consists of four ... ERBB is abbreviated from erythroblastic oncogene B, a gene originally isolated from the avian genome. The human protein is also ...
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 ...
... "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 ...
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 ...
EVI1 is a proto-oncogene conserved across humans, mice, and rats, sharing 91% homology in nucleotide sequence and 94% homology ... MDS1 and EVI1 complex locus protein EVI1 (MECOM) also known as ecotropic virus integration site 1 protein homolog (EVI-1) or ... and taxol-mediated cell death via PI3K/AKT". Oncogene. 25 (25): 3565-75. doi:10.1038/sj.onc.1209403. PMID 16462766. Alliston T ... EVI1 has been described as a proto-oncogene since its first discovery in 1988. Overexpression and aberrant expression of EVI1 ...
Alexiadis V, Waldmann T, Andersen J, Mann M, Knippers R, Gruss C (2000). "The protein encoded by the proto-oncogene DEK changes ... The binding of these proteins to nuclear speckled domains has been measured recently and it may be regulated by PI3K/AKT/mTOR ... 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 ...
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: ...
... 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 ... Skp2 behaves as an oncogene in cell systems and is an established protooncogene causally involved in the pathogenesis of ... and evidence suggests that Skp2 plays a proto-oncogenic role both in vitro and in vivo. Skp2 overexpression has been seen in: ...
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 ...
Franke TF, Kaplan DR, Cantley LC, Toker A (January 1997). "Direct regulation of the Akt proto-oncogene product by ... This approach was used to characterize the substrate specificity of a large number of protein kinases. The kinase specificity ... 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 ... They further demonstrated that tuberin/TSC2 is a critical substrate of AKT, and together with the laboratory of John Blenis ...
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 ...
Mutations in the K-ras proto-oncogene contribute to roughly 10-30% of lung adenocarcinomas. Nearly 4% of non-small-cell lung ... New approaches target protein or glycoprotein markers that are specific to the stem cells. Such markers include CD133, CD90, ... This may occur through the activation of signaling pathways such as Akt/GSK3Beta, MEK-ERK, Fas, and Par6. Smoking prevention ... Up to 7% of those with NSCLC harbor mutations that result in hyperactive ALK protein, which can be treated with ALK inhibitors ...
... has been shown to have a physical interaction with proto-oncogene Myc by tandem affinity purification. 68 orthologs are ... C2orf16 is a protein that in humans is encoded by the C2orf16 gene. Isoform 2 of this protein (NCBI ID: CAH18189.1 henceforth ... "Akt inhibitors MK-2206 and nelfinavir overcome mTOR inhibitor resistance in diffuse large B-cell lymphoma". Clinical Cancer ... "hypothetical protein [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-05-02. "C2orf16 Gene". GeneCards ...
Proto-oncogene c-KIT is the gene encoding the receptor tyrosine kinase protein known as tyrosine-protein kinase KIT, CD117 ( ... Jahn T, Seipel P, Urschel S, Peschel C, Duyster J (February 2002). "Role for the adaptor protein Grb10 in the activation of Akt ... KIT is a proto-oncogene, meaning that overexpression or mutations of this protein can lead to cancer. Seminomas, a subtype of ... Proto-Oncogene+Proteins+c-kit at the US National Library of Medicine Medical Subject Headings (MeSH) C-kit receptor entry in ...
"WD Repeat Protein WDR48 in Complex with Deubiquitinase USP12 Suppresses Akt-dependent Cell Survival Signaling by Stabilizing PH ... "PNUTS Functions as a Proto-Oncogene by Sequestering PTEN". Cancer Research. 73 (1): 205-214. doi:10.1158/0008-5472.CAN-12-1394 ... The team led by Reddy is credited with the identification of NEDD4-like E3 ubiquitin-protein ligase WWP2, an E3 ligase, as a ... "Protein promise for cancer". Nature India. 2011-05-04. doi:10.1038/nindia.2011.65. "Subbareddy Maddika - Google Scholar ...
RAF proto-oncogene serine/threonine-protein kinase, also known as proto-oncogene c-RAF or simply c-Raf or even Raf-1, is an ... Zimmermann S, Moelling K (November 1999). "Phosphorylation and regulation of Raf by Akt (protein kinase B)". Science. 286 (5445 ... RAF proto-oncogene serine/threonine-protein kinase) at the PDBe-KB. Portal: Biology (Articles with short description, Short ... "The small GTP-binding protein, Rhes, regulates signal transduction from G protein-coupled receptors". Oncogene. 23 (2): 559-68 ...
PELP1 is a proto-oncogene that provides cancer cells with a distinct growth and survival advantage. PELP1 interacts with ... The PELP1 protein encodes a protein of 1130 amino acids, and exhibits both cytoplasmic and nuclear localization depending on ... Altered localization of PLP1 contributes to tamoxifen resistance via excessive activation of the AKT pathway and cytoplasmic ... PELP1 is a proto-oncogene that provides cancer cells with a distinct growth and survival advantage. PELP1 overexpression has ...
"Novel BTB/POZ domain zinc-finger protein, LRF, is a potential target of the LAZ-3/BCL-6 oncogene". Oncogene. 18 (2): 365-75. ... Jardin F, Ruminy P, Bastard C, Tilly H (February 2007). "The BCL6 proto-oncogene: a leading role during germinal center ... "Quantitative Proteomics Reveals that miR-155 Regulates the PI3K-AKT Pathway in Diffuse Large B-Cell Lymphoma". The American ... "Colocalization and heteromerization between the two human oncogene POZ/zinc finger proteins, LAZ3 (BCL6) and PLZF". Oncogene. ...
... may be hijacked by viral proteins (for example, by UL56 from Herpes simplex virus 2, or by protein VP40 from Ebola virus ... Fan CD, Lum MA, Xu C, Black JD, Wang X (2013). "Ubiquitin-dependent regulation of phospho-AKT dynamics by the ubiquitin E3 ... Oncogene. 34 (9): 1105-15. doi:10.1038/onc.2014.56. PMID 24662824. S2CID 28296461. Lin Q, Wang J, Childress C, Sudol M, Carey ... "NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN". Cell. 128 (1): 129-39. doi:10.1016/j.cell.2006.11.039. PMC 1828909. ...
"Proto-Oncogene Proteins c-akt/*metabolism". Regulation of cardiac hypertrophic signaling by prolyl isomerase Pin1.. RATIONALE: ... Although Akt is known to be a crucial signaling protein in the myocardium, the role of Pim-1 has been overlooked. Pim-1 ... Pim-1 regulates cardiomyocyte survival downstream of Akt.. The serine-threonine kinases Pim-1 and Akt regulate cellular ... selectively dephosphorylates Akt at Ser473 and terminates Akt signaling in cancer cells. The regulatory role of PHLPP-1 in the ...
... related protein 3 (DKK3), which is a member of the Dickkopf WNT signaling pathway inhibitor family, is considered to be a tumor ... Proto-Oncogene Proteins c-akt / genetics * Proto-Oncogene Proteins c-akt / metabolism* ... In addition, in HSC‑3 shDKK3 cells, the expression levels of phosphorylated (p)‑protein kinase B (Akt) (Ser473), p‑ ... Keywords: head and neck squamous cell carcinoma; Dickkopfrelated protein 3; phosphoinositide 3-kinase; protein kinase B; ...
Proto-Oncogene Proteins c-akt. Zhang W-J, Wei H, Hagen T, Frei B. 2007. Alpha-lipoic acid attenuates LPS-induced inflammatory ... Protein Phosphatase 2. Smith AR, Visioli F, Frei B, Hagen TM. 2006. Age-related changes in endothelial nitric oxide synthase ... Protein Structure, Tertiary. Sowell J, Frei B, Stevens JF. 2004. Vitamin C conjugates of genotoxic lipid peroxidation products ... Protein Conformation. Sowell J, Frei B, Stevens JF. 2004. Vitamin C conjugates of genotoxic lipid peroxidation products: ...
Protein Interaction Domains and Motifs. 1. 2014. 522. 0.030. Why? Proto-Oncogene Proteins c-akt. 1. 2020. 2593. 0.030. Why? ... Proto-Oncogene Proteins. 1. 2022. 4689. 0.090. Why? Calcium-Binding Proteins. 1. 2013. 1101. 0.090. Why? ...
Proto-Oncogene Proteins c-akt/metabolism, Proton Pump Inhibitors/toxicity, Receptor, ErbB-2/metabolism, Signal Transduction", ... Mitogen-Activated Protein Kinase 1/metabolism, Mitogen-Activated Protein Kinase 3/metabolism, Neoplasms, Hormone-Dependent/ ... Furthermore, OME induced the phosphorylation of MAPK-ERK1/2, PI3K/Akt and GSK-3β, and blunted the expression and activity of ... Furthermore, OME induced the phosphorylation of MAPK-ERK1/2, PI3K/Akt and GSK-3β, and blunted the expression and activity of ...
... proto-oncogene proteins c-akt, risk factors, treatment outcome",. author = "Howell, {Neil J} and Houman Ashrafian and Drury, { ... keywords = "AMP-activated protein kinases, acetylglucosamine, aged, aortic valve, aortic valve stenosis, cardiac output, low, ...
Phosphorylation of Akt at Thr308 and Ser473 activates the kinase following growth factor stimulation. Delineating specific role ... We found that phosphorylation at Ser473 provided resistance to chemical inhibition by the Akt inhibitor Akti-1/2. Finally, we ... The proto-oncogene Akt/protein kinase B plays a pivotal role in cell growth and survival. ... The proto-oncogene Akt/protein kinase B plays a pivotal role in cell growth and survival. Phosphorylation of Akt at Thr308 and ...
The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. Cell. ... A proto-oncogene is a normal gene that can convert to an oncogene due to mutations (generally dominant mutations) or increased ... Mutations in proto-oncogene can either create an oncogene or lead to a cascade of inactivation of several more tumor suppressor ... A proto-oncogene can convert into an oncogene due to various reasons including chromosomal translocation (such as BCR-ABL that ...
Proto-Oncogene Proteins c-akt. dc.subject. Clinical Trials, Phase I as Topic. ... infection when compared with single-agent PI3K-AKT-mTOR inhibitors.Conclusions Inhibitors of the PI3K-AKT-mTOR pathway can be ... Combinations of PI3K-AKT-mTOR inhibitors and cytotoxic chemotherapy significantly increase the risk of infection. This should ... We also collected data from 42 patients who were treated with phase I trials of combinations of PI3K-AKT-mTOR inhibitors and ...
Proto-Oncogene Proteins c-akt 100% * Genistein 99% * Transcription Factor AP-1 93% ... activator protein-1 and promotes cell mineralisation. Liao, M. H., Tai, Y-T., Cherng, Y-G., Liu, S. H., Chang, Y. A., Lin, P. I ... Genistein induces oestrogen receptor-α gene expression in osteoblasts through the activation of mitogen-activated protein ... Pulsed radiofrequency inhibited activation of spinal mitogen-activated protein kinases and ameliorated early neuropathic pain ...
Proto-Oncogene Proteins c-akt 100% * Catalytic Domain 75% * Protein Kinase C 39% ... Protein kinases, from B to C. Cameron, A. J., De Rycker, M., Calleja, V., Alcor, D., Kjaer, S., Kostelecky, B., Saurin, A., ... Screening a protein kinase inhibitor library against Plasmodium falciparum. Hallyburton, I., Grimaldi, R., Woodland, A., ... Simulation of protein-sugar interactions: A computational model of the complex between ganglioside GM1 and the heat-labile ...
AKT1 , AKT , AKT-1 , C-AKT , Pan-AKT , PKB alpha , PKBalpha , Proto-oncogene c-Akt , Protein kinase B , Rac protein kinase ... Proteins All Proteins Recombinant Proteins Native Proteins Over-Expression Lysates Bio-Active Proteins Animal-Free Proteins ... Site Links Home All Antibodies How To Buy All Proteins Distributors All ELISA & Assay Kits Reviews PathPlus™ Antibodies ... Coronavirus Detection Coronavirus and COVID-19 Inhibitors Coronavirus Antibodies, Proteins, and cDNAs Cytokine Release Syndrome ...
Proto-Oncogene Proteins c-akt/metabolism MH - Proto-Oncogene Proteins c-bcl-2/metabolism MH - Rats MH - Rats, Wistar MH - ... Proto-Oncogene Proteins c-akt) RN - EC (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Adenoviridae/ ... Other signaling intermediates (protein kinase C, protein kinase G or protein tyrosine kinase (PTK)) either have negative ... Proto-Oncogene Proteins c-bcl-2) RN - 137497-38-2 (midkine) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC ( ...
akt Proto Oncogene Protein akt Proto-Oncogene Protein c akt Proto Oncogene Protein c-akt Protein c-akt Proto-Oncogene Protein c ... Proto Oncogene Protein Akt Proto Oncogene Protein RAC Proto Oncogene Proteins c akt Proto-Oncogene Protein Akt Proto-Oncogene ... Proto-Oncogene Protein Akt. Proto-Oncogene Protein RAC. Proto-Oncogene Protein, akt. Proto-Oncogene Protein, c-akt. Proto- ... Proto-Oncogene. Proto Oncogene Protein Akt. Proto Oncogene Protein RAC. Proto Oncogene Proteins c akt. Proto Oncogene Proteins ...
The AKT1 gene provides instructions for making a protein called AKT1 kinase. Learn about this gene and related health ... protein kinase B alpha. *proto-oncogene c-Akt. *RAC. *rac protein kinase alpha ... The AKT1 gene belongs to a class of genes known as oncogenes. When mutated, oncogenes have the potential to cause normal cells ... The AKT1 gene provides instructions for making a protein called AKT1 kinase. This protein is found in various cell types ...
Protein Phosphatase 2 97% * Superoxide Dismutase-1 94% * Proto-Oncogene Proteins c-akt 89% ... A novel Akt/PKB-interacting protein promotes cell adhesion and inhibits familial amyotrophic lateral sclerosis-linked mutant ... A DEAD-box RNA helicase Ddx54 protein in oligodendrocytes is indispensable for myelination in the central nervous system. Zhan ... SOD1-induced neuronal death via inhibition of PP2A-mediated dephosphorylation of Akt/PKB. Nawa, M., Kanekura, K., Hashimoto, Y. ...
Proto-Oncogene Proteins c-akt Medicine & Life Sciences 6% View full fingerprint ... N2 - Introduction: The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling ... AB - Introduction: The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling ... Introduction: The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling ...
Proto-Oncogene Proteins c-akt Medicine & Life Sciences 14% View full fingerprint ... Next-generation sequencing of the tumor identified a G469V substitution in serine/threonine-protein kinase B-raf (BRAF). Based ... Next-generation sequencing of the tumor identified a G469V substitution in serine/threonine-protein kinase B-raf (BRAF). Based ... Next-generation sequencing of the tumor identified a G469V substitution in serine/threonine-protein kinase B-raf (BRAF). Based ...
Proto-Oncogene Proteins c-akt; Receptor, Insulin; RNA, Small Interfering; Vascular Endothelial Growth Factor A. ... Oncogene. Volume: 29. Products: *Bioware cell lines. Keywords: Animals; Bioware; Cell Line, Tumor; Cell Proliferation; Female; ... Targeting monocyte chemotactic protein-1 synthesis with bindarit induces tumor regression in prostate and breast cancer animal ... Protein-Serine-Threonine Kinases/genetics/*metabolism; Receptors, Transforming Growth Factor beta/genetics/*metabolism; Signal ...
Proto-Oncogene Proteins c-akt. dc.subject. Ribosomal Protein S6 Kinases, 70-kDa. ... p,Protein kinase B/Akt protein kinases control an array of diverse functions, including cell growth, survival, proliferation, ... Protein kinase B/Akt protein kinases control an array of diverse functions, including cell growth, survival, proliferation, and ... These results indicate that PHLDB1 is a novel modulator of Akt protein kinase activation by insulin.,/p,. ...
Proto-Oncogene Proteins c-akt. Phosphatidylinositol 3-Kinase. TOR Serine-Threonine Kinases ... The phosphoinositide 3-kinase (PI3K)-AKT-mTOR cascade is frequently hyperactivated in cancer, and plays an integral role in ... transaminitis and pneumonitis and the increased incidence of infections with the majority of agents that target the PI3K-AKT- ...
proto-oncogene proteins c-akt (1) TOC Heading. Filter by toc-heading. * Basic Science (1) ...
Proto-Oncogene Proteins c-akt 7% * Phosphoric Monoester Hydrolases 6% * Messenger RNA 3% ...
Proto-Oncogene Proteins c-akt 40% * Palmoplantar Keratoderma 35% * Furin 32% * Orphaned Children 32% ...
Membrane Proteins, Mice, Mouse embryonic fibroblast, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins c-akt, Signal ... Membrane Proteins, Mice, Mouse embryonic fibroblast, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins c-akt, Signal ... Importantly, the AKT inhibitor or dominant negative AKT transfection sensitizes c-FLIP. -/- cells to ER stress-induced cell ... Importantly, the AKT inhibitor or dominant negative AKT transfection sensitizes c-FLIP. -/- cells to ER stress-induced cell ...
EPHB2, Eph receptor B2; SRC, proto-oncogene tyrosine-protein kinase Src; AKT, protein kinase B; GSK3β, glycogen synthase kinase ... Mechanistically, EPHB2 was shown to bind and phosphorylate SRC, leading to the activation of AKT/GSK3β/β-catenin signaling axis ... Left panel) EPHB2 tyrosine kinase receptor binds and activates SRC, activating a downstream AKT/GSK3β/β-catenin signaling axis ... Importantly, silencing EPHB2 in NRAS/AKT-induced HCC mouse models showed greater efficacy in suppressing tumor growth when ...
Proto-Oncogene Proteins c-akt. * Survival Analysis. * Triiodothyronine. * Ultrasonography. * Ventricular Dysfunction. authors ...
Proto-Oncogene Proteins c-akt Medicine & Life Sciences 19% * Extracellular Signal-Regulated MAP Kinases Medicine & Life ... 5-Tri-iodo-l-thyronine stimulated phosphorylation of extracellular signal-regulated kinase and AKT (also known as Protein ... 5-Tri-iodo-l-thyronine stimulated phosphorylation of extracellular signal-regulated kinase and AKT (also known as Protein ... 5-Tri-iodo-l-thyronine stimulated phosphorylation of extracellular signal-regulated kinase and AKT (also known as Protein ...
  • Furthermore, phosphorylation of mechanistic target of rapamycin (mTOR) (Ser2448) was slightly decreased in HSC‑3 shDKK3 cells, which may be due to the increased expression of DEP domain‑containing mTOR‑interacting protein. (nih.gov)
  • Furthermore, OME induced the phosphorylation of MAPK-ERK1/2, PI3K/Akt and GSK-3β, and blunted the expression and activity of cellular prostatic acid phosphatase. (elsevier.com)
  • Phosphorylation of Akt at Thr308 and Ser473 activates the kinase following growth factor stimulation. (uwo.ca)
  • We found that phosphorylation at Ser473 provided resistance to chemical inhibition by the Akt inhibitor Akti-1/2. (uwo.ca)
  • Protein-serine-threonine kinases that contain PLECKSTRIN HOMOLOGY DOMAINS and are activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN . (bvsalud.org)
  • Depletion of PHLDB1 by siRNA inhibited insulin stimulation of Akt phosphorylation but not tyrosine phosphorylation of IRS-1. (umassmed.edu)
  • Furthermore, adenovirus-mediated expression of PHLDB1 in adipocytes enhanced insulin-stimulated Akt and p70 S6 kinase phosphorylation, as well as GLUT4 translocation. (umassmed.edu)
  • 001). 3,3′,5-Tri-iodo-l-thyronine stimulated phosphorylation of extracellular signal-regulated kinase and AKT (also known as Protein Kinase B [PKB]) signaling pathways. (elsevier.com)
  • We find that AKT phosphorylation of NPM-Ser48 prevents oligomerization that results in nucleoplasmic localization of ARF, constitutive MDM2 inhibition and stabilization of p53. (ox.ac.uk)
  • Left ventricular biopsies were analyzed to assess changes in 5' adenosine monophosphate-activated protein kinase (AMPK), Akt phosphorylation, and protein O-linked β-N-acetylglucosamination (O-GlcNAcylation). (ox.ac.uk)
  • These changes were associated with a substantial increase in AMPK and Akt phosphorylation and a significant increase in the O-GlcNAcylation of selected protein bands. (ox.ac.uk)
  • This benefit was associated with increased signaling protein phosphorylation and O-GlcNAcylation. (ox.ac.uk)
  • Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. (cusabio.com)
  • Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. (cusabio.com)
  • AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). (cusabio.com)
  • AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. (cusabio.com)
  • AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. (cusabio.com)
  • The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. (cusabio.com)
  • The expression of cell adhesion molecules (ICAM-1and VCAM-1) and the activation of signal transduction pathways (nuclear factor (NF)-κB, mitogen-activated protein kinases (MAPKs) and protein kinase B (Akt)) in HPDLCs were detected by Western blot analysis. (tokushima-u.ac.jp)
  • These findings indicate that nobiletin could inhibit inflammatory reactions in IL-1β-stimulated HPDLCs by inhibiting multiple signal transduction pathways, including NF-κB, MAPKs, and Akt. (tokushima-u.ac.jp)
  • The serine-threonine kinases Pim-1 and Akt regulate cellular proliferation and survival. (glembotskilab.org)
  • Protein kinase B/Akt protein kinases control an array of diverse functions, including cell growth, survival, proliferation, and metabolism. (umassmed.edu)
  • AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. (cusabio.com)
  • Protein Serine-threonine kinases that phosphorylate the 63-kDa subunit of AMP-ACTIVATED PROTEIN KINASES . (nih.gov)
  • In addition, in HSC‑3 shDKK3 cells, the expression levels of phosphorylated (p)‑protein kinase B (Akt) (Ser473), p‑phosphoinositide 3‑kinase (PI3K) p85 (Tyr467), p‑PI3K p55 (Try199), p‑3‑phosphoinositide‑dependent protein kinase‑1 (PDK1) (Ser241) and total p38 mitogen‑activated protein kinase (MAPK) were reduced. (nih.gov)
  • These data supported the hypothesis and indicated that DKK3 may contribute to the malignant phenotype of HNSCC cells via the PI3K/Akt/mTOR and MAPK signaling pathways. (nih.gov)
  • Higher Risk of Infections with PI3K-AKT-mTOR Pathway Inhibitors in Patients with Advanced Solid Tumors on Phase I Clinical Trials. (icr.ac.uk)
  • Purpose Novel antitumor therapies against the PI3K-AKT-mTOR pathway are increasingly used to treat cancer, either as single agents or in combination with chemotherapy or other targeted therapies. (icr.ac.uk)
  • P = 0.03) infection when compared with single-agent PI3K-AKT-mTOR inhibitors.Conclusions Inhibitors of the PI3K-AKT-mTOR pathway can be associated with a higher risk of infection. (icr.ac.uk)
  • Combinations of PI3K-AKT-mTOR inhibitors and cytotoxic chemotherapy significantly increase the risk of infection. (icr.ac.uk)
  • This should be taken into consideration during the design and conduct of trials involving PI3K-AKT-mTOR pathway inhibitors, particularly when combined with chemotherapy or myelosuppressive agents. (icr.ac.uk)
  • Introduction: The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway plays a central role in regulating cell growth and proliferation and thus has been considered as effective anticancer drug targets. (nebraska.edu)
  • ROS1 fusion proteins result in constitutive ROS1 kinase activity leading to upregulation of downstream signaling pathways including MAPK , PI3K / AKT and JAK pathways known to play a role in malignant transformation. (healio.com)
  • The phosphoinositide 3-kinase (PI3K)-AKT-mTOR cascade is frequently hyperactivated in cancer, and plays an integral role in many cellular processes including tumour growth and survival and can underlie resistance to therapies. (icr.ac.uk)
  • In this review, we first summarize two key learnings from the initial studies of inhibitors of this pathway, including the profile of immune-related adverse events such as colitis, transaminitis and pneumonitis and the increased incidence of infections with the majority of agents that target the PI3K-AKT-mTOR pathway. (icr.ac.uk)
  • We demonstrate that AKT and PI3K inhibitors may be effective in treatment of therapeutically resistant tumors with elevated AKT and carrying gain of function mutations in p53. (ox.ac.uk)
  • Critically, we propose that combination therapy involving PI3K-AKT inhibitors would benefit from a patient stratification rationale based on ARF and p53(mut) status. (ox.ac.uk)
  • Here, we discuss experimental evidence that argues for a critical role of the PI3K-phosphoinositide-dependent protein kinase (PDK1)-protein kinase B (PKB) signaling pathway in the development of both normal and malignant thymocytes, and we highlight molecules that can potentially be targeted therapeutically. (ox.ac.uk)
  • Dickkopf‑related protein 3 (DKK3), which is a member of the Dickkopf WNT signaling pathway inhibitor family, is considered to be a tumor suppressor, due to its reduced expression in cancer cells and its ability to induce apoptosis when overexpressed by adenovirus. (nih.gov)
  • Alpha-lipoic acid attenuates LPS-induced inflammatory responses by activating the phosphoinositide 3-kinase/Akt signaling pathway. (oregonstate.edu)
  • The sonic hedgehog signaling pathway stimulates anaplastic thyroid cancer cell motility and invasiveness by activating Akt and c-Met. (uchicago.edu)
  • Williamson AJ, Doscas ME, Ye J, Heiden KB, Xing M, Li Y, Prinz RA, Xu X. The sonic hedgehog signaling pathway stimulates anaplastic thyroid cancer cell motility and invasiveness by activating Akt and c-Met. (uchicago.edu)
  • Cellular-Flice-like inhibitory protein (c-FLIP) is an apoptosis modulator known to inhibit the extrinsic apoptotic pathway thus blocking Caspase-8 processing in the Death Inducing Signalling Complex (DISC). (unicatt.it)
  • In addition, inhibition of Akt enhanced ER stress-induced macrophage apoptosis, and expression of a constitutively active myristoylated Akt blocked the enhancement of ER stress-induced apoptosis that occurred with p38 inhibition in cultured cells. (duke.edu)
  • Mechanistically, AGGF1 interacts with TWEAK (tumour necrosis factor-like weak inducer of apoptosis), which reduces interaction between TWEAK and its receptor Fn14 (fibroblast growth factor-inducing protein 14). (bvsalud.org)
  • Role of the kinase MST2 in suppression of apoptosis by the proto-oncogene product Raf-1. (idrblab.net)
  • This protein is found in various cell types throughout the body, where it plays a critical role in many signaling pathways. (medlineplus.gov)
  • Analysis of Unfolded Protein Response (UPR) pathways revealed that Pancreatic ER Kinase (PERK) and Inositol-Requiring Enzyme 1 (IRE1) branch signalling is compromised in c-FLIP. (unicatt.it)
  • Moreover, we found that 6-MSITC could suppress signal transducer and activator of transcription (STAT)3, nuclear factor (NF)-κB, and p70S6 kinase (p70S6K)-S6 ribosomal protein (S6) pathways activation in TNF-α-stimulated TR146 cells. (tokushima-u.ac.jp)
  • Moreover, we revealed that nobiletin treatment could suppress the activation of the NF-κB, MAPKs, and Akt pathways. (tokushima-u.ac.jp)
  • cells to ER stress-induced cell death while the expression of a constitutively active AKT reduces WT cells sensitivity to ER stress-induced death. (unicatt.it)
  • This action results in reactivation of AMP-ACTIVATED PROTEIN KINASE activity and downstream signaling aimed at decreased metabolism. (nih.gov)
  • KEGG pathway analysis showed that the proteins were mainly involved in transport and metabolism, immune system, cancer, membrane transport and other processes. (bvsalud.org)
  • The AKT1 gene belongs to a class of genes known as oncogenes. (medlineplus.gov)
  • These mutations are the result of rearrangements of ROS1 with other genes forming fusion proteins. (healio.com)
  • Our results show that the clinical candidate AKT inhibitor MK-2206 promotes ARF nucleolar localization, reduced p53(mut) stability and increased sensitivity to ionizing radiation in a xenograft model of pancreatic cancer. (ox.ac.uk)
  • Pharmacological inhibition or genetic ablation of p38 suppressed activation of Akt in cultured macrophages and in atherosclerotic lesions. (duke.edu)
  • Tumors with amplification also demonstrated an increase in phospho-p70S6K but had decreased levels of activated phospho-AKT1-3 as assessed by Reverse Phase Protein Arrays and an mRNA signature of MTOR inhibition.CONCLUSIONS: amplification is a strong prognostic marker and a potential marker for the aggressive SCNA-high subgroup of UCEC. (broadinstitute.org)
  • AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. (cusabio.com)
  • It is a natural taxane, and it prevents depolymerization of cellular microtubules, which results in DNA, RNA, and protein synthesis inhibition. (medscape.com)
  • Next-generation sequencing of the tumor identified a G469V substitution in serine/threonine-protein kinase B-raf (BRAF). (elsevier.com)
  • We found that c-FLIP modulates the PERK pathway by interfering with the activity of the serine threonine kinase AKT. (unicatt.it)
  • Death-associated protein kinase 1 (DAPK1) is a large multidomain protein with an N-terminal serine/threonine protein kinase domain. (iucr.org)
  • Death-associated protein kinase 1 (DAPK1) is a Ca 2+ /calmodulin-regulated serine/threonine protein kinase (CaMK) composed of an N-terminal catalytic kinase domain, a Ca 2+ /calmodulin-binding domain, ankyrin repeats, an Roc/COR domain and a death domain. (iucr.org)
  • The AKT1 gene provides instructions for making a protein called AKT1 kinase. (medlineplus.gov)
  • This mutation changes a single protein building block (amino acid) in AKT1 kinase. (medlineplus.gov)
  • Amplification Associates with Aggressive Phenotype but Not Markers of AKT-MTOR Signaling in Endometrial Carcinoma. (broadinstitute.org)
  • PKB/Akt: connecting phosphoinositide 3-kinase to cell survival and beyond. (wikidata.org)
  • Expression of IpgD, a PtdIns(4,5)P(2) 4-phosphatase induces Src kinase and Akt, but not ERK activation and enhances interleukin II promoter activity in T-cells. (ox.ac.uk)
  • The cardioprotective effect of a statin and cilostazol combination: relationship to Akt and endothelial nitric oxide synthase activation. (uams.edu)
  • Manickavasagam S, Ye Y, Lin Y, Perez-Polo RJ, Huang MH, Lui CY, Hughes MG, McAdoo DJ, Uretsky BF, Birnbaum Y. The cardioprotective effect of a statin and cilostazol combination: relationship to Akt and endothelial nitric oxide synthase activation. (uams.edu)
  • RATIONALE: The recently discovered PHLPP-1 (PH domain leucine-rich repeat protein phosphatase-1) selectively dephosphorylates Akt at Ser473 and terminates Akt signaling in cancer cells. (glembotskilab.org)
  • Cadmium-induced cell transformation and tumorigenesis are associated with transcriptional activation of c-fos, c-jun and c-myc proto-oncogenes: role of cellular calcium and reactive oxygen species. (cdc.gov)
  • PHLPP-1 negatively regulates Akt activity and survival in the heart. (glembotskilab.org)
  • Pim-1 regulates cardiomyocyte survival downstream of Akt. (glembotskilab.org)
  • AKT regulates NPM dependent ARF localization and p53mut stability in tumors. (ox.ac.uk)
  • AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein). (cusabio.com)
  • Importantly, the AKT inhibitor or dominant negative AKT transfection sensitizes c-FLIP. (unicatt.it)
  • Regulation of proapoptotic mammalian ste20-like kinase MST2 by the IGF1-Akt pathway. (idrblab.net)
  • Protein interaction network of the mammalian Hippo pathway reveals mechanisms of kinase-phosphatase interactions. (idrblab.net)
  • Analysis of human tumors indicates that phospho-S48-NPM may be a useful biomarker for monitoring AKT activity and in vivo efficacy of AKT inhibitor treatment. (ox.ac.uk)
  • Transforming activity and mitosis-related expression of the AKT2 oncogene: evidence suggesting a link between cell cycle regulation and oncogenesis. (wikidata.org)
  • Responses to DNA damage and regulation of cell cycle checkpoints by the ATM protein kinase family. (wikidata.org)
  • AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. (cusabio.com)
  • The abnormally active protein disrupts a cell's ability to regulate its own growth, allowing the cell to grow and divide abnormally. (medlineplus.gov)
  • They also regulate SONIC HEDGEHOG PROTEIN signaling and cell proliferation. (nih.gov)
  • v-akt protein is the viral homologue of PROTO-ONCOGENE PROTEINS C-AKT. (jefferson.edu)
  • We report here the identification of pleckstrin homology-like domain family B member 1 (PHLDB1) as an insulin-responsive protein that enhances Akt activation. (umassmed.edu)
  • Adding a carrier protein enhances protein stability, increases shelf-life, and allows the recombinant protein to be stored at a more dilute concentration. (rndsystems.com)
  • AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. (cusabio.com)
  • Atrial natriuretic peptide promotes cardiomyocyte survival by cGMP-dependent nuclear accumulation of zyxin and Akt. (glembotskilab.org)
  • The proto-oncogene Akt/protein kinase B plays a pivotal role in cell growth and survival. (uwo.ca)
  • Oncogene Protein v-akt" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (jefferson.edu)
  • Proto-Oncogene Proteins c-pim-1" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (uchicago.edu)
  • Expression of PIM1 protein in chronic lymphocytic leukemia/small lymphocytic lymphoma. (uchicago.edu)
  • Majewski M, Nieborowska-Skorska M, Salomoni P, Slupianek A, Reiss K, Trotta R, Calabretta B, Skorski T. Activation of mitochondrial Raf-1 is involved in the antiapoptotic effects of Akt. (jefferson.edu)
  • These results indicate that PHLDB1 is a novel modulator of Akt protein kinase activation by insulin. (umassmed.edu)