Recombinant Mouse Phosphatidylinositol 3-kinase regulatory subunit alpha (Pik3r1)

Function

Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues (PubMed:27708159). Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling (By similarity). Modulates the cellular response to ER stress by promoting 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 (PubMed:20348926)

Subcellular Location

Cytoplasm

Subunit

Heterodimer of a regulatory subunit PIK3R1 and a p110 catalytic subunit (PIK3CA, PIK3CB or PIK3CD). Interacts (via SH2 domains) with CCDC88A/GIV (tyrosine-phosphorylated form); the interaction enables recruitment of PIK3R1 to the EGFR receptor, enhancing PI3K activity and cell migration (By similarity). 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 (PubMed:20348926). Interacts with PIK3R2; the interaction is dissociated in an insulin-dependent manner (PubMed:20348926). Interacts with phosphorylated LAT, LAX1 and TRAT1 upon TCR activation. The SH2 domains interact with the YTHM motif of phosphorylated INSR in vitro. Also interacts with tyrosine-phosphorylated IGF1R in vitro. Interacts with IRS1, IRS2 and phosphorylated IRS4, as well as with NISCH and HCST (By similarity). Interacts with phosphorylated TOM1L1. Interacts with phosphorylated LIME1 upon TCR or BCR activation. Interacts with CBLB. Interacts with CD28 and CD3Z upon T-cell activation. Interacts with SOCS7 and HCST. Interacts with AXL, FASLG, FGR, HCK, KIT and BCR. Interacts with PTK2/FAK1 (By similarity). Interacts with PDGFRB (tyrosine phosphorylated) (By similarity). Interacts with NTRK1 (phosphorylated upon ligand-binding) (By similarity). Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated) (PubMed:9312046). Interacts with FER. Interacts with FGFR1, FGFR2, FGFR3 and FGFR4 (phosphorylated) (Probable). Interacts with PDGFRA (tyrosine phosphorylated). Interacts with LYN (via SH3 domain); this enhances enzyme activity. Interacts with ERBB4. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated). Interacts with FAM83B; activates the PI3K/AKT signaling cascade (By similarity). Interacts with APPL1 and APPL2 (PubMed:25328665). Interacts with SRC (By similarity). Interacts with ALOX5; this interaction bridges ALOX5 with CD40 after CD40 ligation in B cells and leads to the production of reactive oxygen species (ROS) (By similarity). Interacts with TYK2 (By similarity). Interacts with nephrin NPHN1; the interaction is reduced by high glucose levels (By similarity). Interacts with CD28 (By similarity). Interacts with ICOS (PubMed:19915142)

• Escobedo J.A. et al. cDNA cloning of a novel 85 kd protein that has SH2 domains and regulates binding of PI3-kinase to the PDGF beta-receptor. — Cell (1991)
• Mural R.J. et al. PubMed: CI-70VOB8UOSDVQL (SEP-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Yu J.C. et al. Tyrosine mutations within the alpha platelet-derived growth factor receptor kinase insert domain abrogate receptor-associated phosphatidylinositol-3 kinase activity without affecting mitogenic or chemotactic signal transduction. — Mol. Cell. Biol. (1991)
• Pleiman C.M. et al. Activation of phosphatidylinositol-3' kinase by Src-family kinase SH3 binding to the p85 subunit. — Science (1994)
• Bazenet C.E. et al. Phosphorylation of tyrosine 720 in the platelet-derived growth factor alpha receptor is required for binding of Grb2 and SHP-2 but not for activation of Ras or cell proliferation. — Mol. Cell. Biol. (1996)
• Bourette R.P. et al. Sequential activation of phoshatidylinositol 3-kinase and phospholipase C-gamma2 by the M-CSF receptor is necessary for differentiation signaling. — EMBO J. (1997)
• Jones N. et al. Identification of Tek/Tie2 binding partners. Binding to a multifunctional docking site mediates cell survival and migration. — J. Biol. Chem. (1999)