AKT3   단백질

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AKT3  요약 및 단백질 정보

AKT3  배경

유전자 요약: The protein encoded by this gene 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 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),and IGF1. Alternatively splice transcript variants encoding distinct isoforms have been described
General information above from NCBI
촉매 활성: ATP + a protein = ADP + a phosphoprotein.
효소 조절: ENZYME REGULATION: Two specific sites, one in the kinase domain (Thr-305) and the other in the C-terminal regulatory region (Ser-472), need to be phosphorylated for its full activation (By similarity). IGF-1 leads to the activation of AKT3, which may play a role in regulating cell survival. {ECO:0000250}.
하부단위 구조: Interacts (via PH domain) with TCL1A; this enhances AKT3 phosphorylation and activation. Interacts with TRAF6. Interacts with KCTD20 (By similarity). Interacts with BTBD10 (By similarity). {ECO:0000250|UniProtKB:Q9WUA6, ECO:0000269|PubMed:11707444, ECO:0000269|PubMed:11839817, ECO:0000269|PubMed:19713527}.
도메인: Binding of the PH domain to the phosphatidylinositol 3-kinase alpha (PI(3)K) results in its targeting to the plasma membrane.
세포하 위치: Nucleus {ECO:0000269|PubMed:20018949}. Cytoplasm {ECO:0000269|PubMed:20018949}. Membrane {ECO:0000269|PubMed:20018949}; Peripheral membrane protein {ECO:0000269|PubMed:20018949}. Note=Membrane-associated after cell stimulation leading to its translocation.
조직 특이성: In adult tissues, it is highly expressed in brain, lung and kidney, but weakly in heart, testis and liver. In fetal tissues, it is highly expressed in heart, liver and brain and not at all in kidney.
번역 후: Phosphorylation on Thr-305 and Ser-472 is required for full activity. {ECO:0000250}.; Ubiquitinated. When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome. {ECO:0000269|PubMed:12162751, ECO:0000269|PubMed:20059950, ECO:0000269|PubMed:9512493}.; O-GlcNAcylation at Thr-302 and Thr-309 inhibits activating phosphorylation at Thr-305 via disrupting the interaction between AKT and PDK1. {ECO:0000250}.
질병과의 관련성: DISEASE: Note=AKT3 is a key modulator of several tumors like melanoma, glioma and ovarian cancer. Active AKT3 increases progressively during melanoma tumor progression with highest levels present in advanced-stage metastatic melanomas. Promotes melanoma tumorigenesis by decreasing apoptosis. Plays a key role in the genesis of ovarian cancers through modulation of G2/M phase transition. With AKT2, plays a pivotal role in the biology of glioblastoma.; DISEASE: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 (MPPH2) [MIM:615937]: A syndrome characterized by megalencephaly, hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome. {ECO:0000269|PubMed:22500628, ECO:0000269|PubMed:22729223, ECO:0000269|PubMed:22729224}. Note=The disease is caused by mutations affecting the gene represented in this entry.
염기서열 유사성: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily. {ECO:0000305}.; Contains 1 AGC-kinase C-terminal domain. {ECO:0000305}.; Contains 1 PH domain. {ECO:0000255|PROSITE-ProRule:PRU00145}.; Contains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}.
General information above from UniProt

v-akt murine thymoma viral oncogene homolog 3 (AKT3), also known as PKB-GAMMA, with AKT1/PKBalpha, AKT2/PKBbeta, are the memerbers of Akt kinase family, share extensive structural similarity and perform common as well as unique functions within cells. The Akt signaling cascade initiates at the cell surface when growth factors or other extracellular stimuli activate phosphoinositide 3-kinase (PI3K). AKT3 was discovered to be the predominant isoform activated in sporadic melanomas. Levels of activity increased during melanoma progression with metastatic melanomas having the highest activity. Although mechanisms of AKT3 activation remain to be fully characterized, overexpression of AKT3 and decreased PTEN activity play important roles in this process. Targeted reduction of AKT3 activity decreased survival of melanoma tumor cells leading to inhibition of tumor development, which may be therapeutically effective for shrinking tumors in melanoma patients. AKT2 and AKT3 play an important role in the viability of human malignant glioma cells. Targeting AKT2 and AKT3 may hold promise for the treatment of patients with gliomas.

AKT3  대체 이름

MPPH,PKBG,MPPH2,PRKBG,STK-2,PKB-GAMMA,RAC-gamma,RAC-PK-gamma, [homo-sapiens]
AKT3,DKFZp434N0250,PKBG,PKB-GAMMA,PRKBG,RAC-gamma,RAC-PK-gamma,STK-2, [human]
Akt3,D930002M15Rik,I851531, [mouse]
Nmf350,AI851531,D930002M15Rik, [mus-musculus]

AKT3  관련 연구

  • Mure H, et al. (2010) Akt2 and Akt3 play a pivotal role in malignant gliomas. Neuro Oncol. 12(3): 221-32.
  • Koseoglu S, et al. (2007) AKT1, AKT2 and AKT3-dependent cell survival is cell line-specific and knockdown of all three isoforms selectively induces apoptosis in 20 human tumor cell lines. Cancer Biol Ther. 6(5): 755-62.
  • Cristiano BE, et al. (2006) A specific role for AKT3 in the genesis of ovarian cancer through modulation of G(2)-M phase transition. Cancer Res. 66(24): 11718-25.
  • Robertson GP. (2005) Functional and therapeutic significance of Akt deregulation in malignant melanoma. Cancer Metastasis Rev. 24(2): 273-85.
  • Altomare DA, et al. (2005) Perturbations of the AKT signaling pathway in human cancer. Oncogene. 24: 7455-64.
  • Stahl JM, et al. (2004) Deregulated Akt3 activity promotes development of malignant melanoma. Cancer Res. 64: 7002-10.
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