Recombinant Human Phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2), partial

Function

Regulatory subunit of phosphoinositide-3-kinase (PI3K), a kinase that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Binds to activated (phosphorylated) protein-tyrosine kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Indirectly regulates autophagy (PubMed:23604317). Promotes nuclear translocation of XBP1 isoform 2 in a ER stress- and/or insulin-dependent manner during metabolic overloading in the liver and hence plays a role in glucose tolerance improvement (By similarity)

Disease Association

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 (MPPH1) : 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. [The disease is caused by variants affecting the gene represented in this entry]

Subunit

Heterodimer of a regulatory subunit PIK3R2 and a p110 catalytic subunit (PIK3CA, PIK3CB or PIK3CD) (PubMed:23604317). Interacts with AXL (PubMed:9178760). Interacts with FLT1 (tyrosine-phosphorylated) and FLT4 (tyrosine-phosphorylated) (PubMed:15102829, PubMed:9600074). Interacts with NYAP1, NYAP2 and MYO16 (By similarity). Interacts with FBXL2; PIK3R2 is a substrate of the SCF(FBXL2) complex (PubMed:23604317). Interacts with PTPN13; dephosphorylates PIK3R2 (PubMed:23604317). Interacts with XBP1 isoform 2; the interaction is direct and induces translocation of XBP1 isoform 2 into the nucleus in a ER stress- and/or insulin-dependent but PI3K-independent manner (By similarity). Interacts with PIK3R1; the interaction is dissociated in an insulin-dependent manner (By similarity). Interacts with SRC (PubMed:28903391)

• Volinia S. et al. Chromosomal localization of human p85 alpha, a subunit of phosphatidylinositol 3-kinase, and its homologue p85 beta. — Oncogene (1992)
• Janssen J.W.G. et al. An oncogenic fusion product of the phosphatidylinositol 3-kinase p85beta subunit and HUMORF8, a putative deubiquitinating enzyme. — Oncogene (1998)
• Grimwood J. et al. The DNA sequence and biology of human chromosome 19. — Nature (2004)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Braunger J. et al. Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is mediated mainly by a multi-substrate docking-site. — Oncogene (1997)
• Igarashi K. et al. Tyrosine 1213 of Flt-1 is a major binding site of Nck and SHP-2. — Biochem. Biophys. Res. Commun. (1998)
• Wang J.F. et al. Activation of vascular endothelial growth factor receptor-3 and its downstream signaling promote cell survival under oxidative stress. — J. Biol. Chem. (2004)
• Tsuboi N. et al. The tyrosine phosphatase CD148 interacts with the p85 regulatory subunit of phosphoinositide 3-kinase. — Biochem. J. (2008)