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研究背景

The serine-threonine protein kinase encoded by the AKT1 gene is catalytically inactive in serum-starved primary and immortalized fibroblasts. AKT1 and the related AKT2 are activated by platelet-derived growth factor. The activation is rapid and specific, and it is abrogated by mutations in the pleckstrin homology domain of AKT1. It was shown that the activation occurs through phosphatidylinositol 3-kinase. In the developing nervous system AKT is a critical mediator of growth factor-induced neuronal survival. Survival factors can suppress apoptosis in a transcription-independent manner by activating the serine/threonine kinase AKT1, which then phosphorylates and inactivates components of the apoptotic machinery. Mutations in this gene have been associated with the Proteus syndrome. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2011]catalytic activity:ATP + a protein = ADP + a phosphoprotein.,disease:Defects in AKT1 are associated with breast cancer (BC) [MIM:114480]. BC is an extremely common malignancy, affecting one in eight women during their lifetime.,disease:Defects in AKT1 are associated with colorectal cancer (CRC) [MIM:114500].,disease:Defects in AKT1 are associated with susceptibility to ovarian cancer [MIM:604370]; also called susceptibility to familial breast-ovarian cancer type 1 (BROVCA1).,domain:Binding of the PH domain to the phosphatidylinositol 3-kinase alpha (PI(3)K) results in its targeting to the plasma membrane.,domain:The AGC-kinase C-terminal mediates interaction with THEM4.,enzyme regulation:Three specific sites, one in the kinase domain (Thr-308) and the two other ones in the C-terminal regulatory region (Ser-473 and Tyr-474), need to be phosphorylated for its full activation.,function:General protein kinase capable of phosphorylating several known proteins. Phosphorylates TBC1D4. Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I). Plays a role in glucose transport by mediating insulin-induced translocation of the GLUT4 glucose transporter to the cell surface. Mediates the antiapoptotic effects of IGF-I. Mediates insulin-stimulated protein synthesis, partly by playing a role in both insulin-induced phosphorylation of 4E-BP1 and in insulin-induced activation of p70 S6 kinase. Promotes glycogen synthesis by mediating the insulin-induced activation of glycogen synthase.,PTM:Phosphorylation on Thr-308, Ser-473 and Tyr-474 is required for full activity. Ser-473 phosphorylation by the Rictor-mTor complex favors Thr-308 phosphorylation by PDPK1. Ser-473 phosphorylation is enhanced by interaction with AGAP2 isoform 2 (PIKE-A). Ser-473 phosphorylation is enhanced in focal cortical dysplasias with Taylor-type balloon cells.,similarity:Belongs to the protein kinase superfamily.,similarity:Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily.,similarity:Contains 1 AGC-kinase C-terminal domain.,similarity:Contains 1 PH domain.,similarity:Contains 1 protein kinase domain.,subcellular location:Nucleus after activation by integrin-linked protein kinase 1 (ILK1). Nuclear translocation is enhanced by interaction with TCL1A.,subunit:Interacts with AGAP2 isoform 2 (PIKE-A) in the presence of guanine nucleotides. The C-terminus interacts with CCDC88A/GRDN and THEM4. Interacts with AKTIP. Interacts (via PH domain) with MTCP1, TCL1A AND TCL1B. Interacts with CDKN1B; the interaction phosphorylates CDKN1B promoting 14-3-3 binding and cell-cycle progression.,tissue specificity:In all human cell types so far analyzed.,

研究領(lǐng)域

Akt_PKB;MAPK_ERK_Growth;MAPK_G_Protein;ErbB_HER;Chemokine;mTOR;Apoptosis_Inhibition;Apoptosis_Mitochondrial;Apoptosis_Overview;VEGF;Focal adhesion;Tight junction;Toll_Like;Jak_STAT;T_Cell_Receptor;B_Cell_Antigen;Fc epsilon RI;Fc gamma R-mediated phagocytosis;Neurotrophin;Insulin_Receptor;Progesterone-mediated oocyte maturation;Adipocytokine;Pathways in cancer;Colorectal cancer;Renal cell carcinoma;Pancreatic cancer;Endometrial cancer;Glioma;Prostate cancer;Melanoma;Chronic myeloid leukemia;Acute myeloid leukemia;Small cell lung cancer;Non-small cell lung cancer;