AKT1/AKT2/AKT3

RAC-alpha serine/threonine-protein kinase;RAC-beta serine/threonine-protein kinase;RAC-gamma serine/threonine-protein kinase

AKT1 gene encodes one of the three members of the human AKT serine-threonine protein kinase family which are often referred to as protein kinase B alpha, beta, and gamma. These highly similar AKT proteins all have an N-terminal pleckstrin homology domain, a serine/threonine-specific kinase domain and a C-terminal regulatory domain. These proteins are phosphorylated by phosphoinositide 3-kinase (PI3K). AKT/PI3K forms a key component of many signalling pathways that involve the binding of membrane-bound ligands such as receptor tyrosine kinases, G-protein coupled receptors, and integrin-linked kinase. These AKT proteins therefore regulate a wide variety of cellular functions including cell proliferation, survival, metabolism, and angiogenesis in both normal and malignant cells. AKT proteins are recruited to the cell membrane by phosphatidylinositol 3,4,5-trisphosphate (PIP3) after phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP2) by PI3K. Subsequent phosphorylation of both threonine residue 308 and serine residue 473 is required for full activation of the AKT1 protein encoded by this gene. Phosphorylation of additional residues also occurs, for example, in response to insulin growth factor-1 and epidermal growth factor. Protein phosphatases act as negative regulators of AKT proteins by dephosphorylating AKT or PIP3. The PI3K/AKT signalling pathway is crucial for tumor cell survival. Survival factors can suppress apoptosis in a transcription-independent manner by activating AKT1 which then phosphorylates and inactivates components of the apoptotic machinery. AKT proteins also participate in the mammalian target of rapamycin (mTOR) signalling pathway which controls the assembly of the eukaryotic translation initiation factor 4F (eIF4E) complex and this pathway, in addition to responding to extracellular signals from growth factors and cytokines, is disregulated in many cancers. Mutations in this gene are associated with multiple types of cancer and excessive tissue growth including Proteus syndrome and Cowden syndrome 6, and breast, colorectal, and ovarian cancers. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2020] AKT2 gene is a putative oncogene encoding a protein belonging to a subfamily of serine/threonine kinases containing SH2-like (Src homology 2-like) domains, which is involved in signaling pathways. The gene serves as an oncogene in the tumorigenesis of cancer cells For example, its overexpression contributes to the malignant phenotype of a subset of human ductal pancreatic cancers. The encoded protein is a general protein kinase capable of phophorylating several known proteins, and has also been implicated in insulin signaling. [provided by RefSeq, Nov 2019] The protein encoded by AKT3 is a member of the AKT, also called PKB, serine/threonine protein kinase family. AKT kinases are known to be regulators of cell signaling in response to insulin and growth factors. They are involved in a wide variety of biological processes including cell proliferation, differentiation, apoptosis, tumorigenesis, as well as glycogen synthesis and glucose uptake. This kinase has been shown to be stimulated by platelet-derived growth factor (PDGF), insulin, and insulin-like growth factor 1 (IGF1). Alternatively splice transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). 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 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. Promotes glycogen synthesis by mediating the insulin-induced activation of glycogen synthase. The activated form can suppress FoxO gene transcription and promote cell cycle progression. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly.

Cytoplasm . Nucleus . Cell membrane . Nucleus after activation by integrin-linked protein kinase 1 (ILK1). Nuclear translocation is enhanced by interaction with TCL1A. Phosphorylation on Tyr-176 by TNK2 results in its localization to the cell membrane where it is targeted for further phosphorylations on Thr-308 and Ser-473 leading to its activation and the activated form translocates to the nucleus. Colocalizes with WDFY2 in intracellular vesicles (PubMed:16792529). .

Expressed in prostate cancer and levels increase from the normal to the malignant state (at protein level). Expressed in all human cell types so far analyzed. The Tyr-176 phosphorylated form shows a significant increase in expression in breast cancers during the progressive stages i.e. normal to hyperplasia (ADH), ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC) and lymph node metastatic (LNMM) stages.

>>EGFR tyrosine kinase inhibitor resistance ;
>>Endocrine resistance ;
>>Platinum drug resistance ;
>>MAPK signaling pathway ;
>>ErbB signaling pathway ;
>>Ras signaling pathway ;
>>Rap1 signaling pathway ;
>>cGMP-PKG signaling pathway ;
>>cAMP signaling pathway ;
>>Chemokine signaling pathway ;
>>HIF-1 signaling pathway ;
>>FoxO signaling pathway ;
>>Sphingolipid signaling pathway ;
>>Phospholipase D signaling pathway ;
>>Autophagy - animal ;
>>mTOR signaling pathway ;
>>PI3K-Akt signaling pathway ;
>>AMPK signaling pathway ;
>>Apoptosis ;
>>Longevity regulating pathway ;
>>Longevity regulating pathway - multiple species ;
>>Cellular senescence ;
>>Adrenergic signaling in cardiomyocytes ;
>>VEGF signaling pathway ;
>>Apelin signaling pathway ;
>>Osteoclast differentiation ;
>>Focal adhesion ;
>>Signaling pathways regulating pluripotency of stem cells ;
>>Platelet activation ;
>>Neutrophil extracellular trap formation ;
>>Toll-like receptor signaling pathway ;
>>C-type lectin receptor signaling pathway ;
>>JAK-STAT signaling pathway ;
>>T cell receptor signaling pathway ;
>>B cell receptor signaling pathway ;
>>Fc epsilon RI signaling pathway ;
>>Fc gamma R-mediated phagocytosis ;
>>TNF signaling pathway ;
>>Neurotrophin signaling pathway ;
>>Cholinergic synapse ;
>>Dopaminergic synapse ;
>>Insulin signaling pathway ;
>>Progesterone-mediated oocyte maturation ;
>>Estrogen signaling pathway ;
>>Prolactin signaling pathway ;
>>Thyroid hormone signaling pathway ;
>>Adipocytokine signaling pathway ;
>>Glucagon signaling pathway ;
>>Regulation of lipolysis in adipocytes ;
>>Relaxin signaling pathway ;
>>GnRH secretion ;
>>Insulin resistance ;
>>Non-alcoholic fatty liver disease ;
>>AGE-RAGE signaling pathway in diabetic complications ;
>>Growth hormone synthesis, secretion and action ;
>>Alcoholic liver disease ;
>>Carbohydrate digestion and absorption ;
>>Alzheimer disease ;
>>Spinocerebellar ataxia ;
>>Shigellosis ;
>>Salmonella infection ;
>>Yersinia infection ;
>>Chagas disease ;
>>Toxoplasmosis ;
>>Tuberculosis ;
>>Hepatitis C ;
>>Hepatitis B ;
>>Measles ;
>>Human cytomegalovirus infection ;
>>Influenza A ;
>>Human papillomavirus infection ;
>>Human T-cell leukemia virus 1 infection ;
>>Kaposi sarcoma-associated herpesvirus infection ;
>>Herpes simplex virus 1 infection ;
>>Epstein-Barr virus infection ;
>>Human immunodeficiency virus 1 infection ;
>>Pathways in cancer ;
>>Proteoglycans in cancer ;
>>Chemical carcinogenesis - receptor activation ;
>>Chemical carcinogenesis - reactive oxygen species ;
>>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 ;
>>Breast cancer ;
>>Hepatocellular carcinoma ;
>>Gastric cancer ;
>>Central carbon metabolism in cancer ;
>>Choline metabolism in cancer ;
>>PD-L1 expression and PD-1 checkpoint pathway in cancer ;
>>Diabetic cardiomyopathy ;
>>Lipid and atherosclerosis ;
>>Fluid shear stress and atherosclerosis