Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform

Function

Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol derivatives at position 3 of the inositol ring to produce 3-phosphoinositides. Uses ATP and 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. Involved in the activation of AKT1 upon stimulation by G protein-coupled receptor (GPCR) ligands such as CXCL12, sphingosine 1-phosphate, and lysophosphatidic acid. May also act downstream receptor tyrosine kinases. Required in different signaling pathways for stable platelet adhesion and aggregation. Plays a role in platelet activation signaling triggered by GPCRs, alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) and ITAM (immunoreceptor tyrosine-based activation motif)-bearing receptors such as GP6. Regulates the strength of adhesion of ITGA2B/ ITGB3 activated receptors necessary for the cellular transmission of contractile forces. Required for platelet aggregation induced by F2 (thrombin) and thromboxane A2 (TXA2). Has a role in cell survival. May have a role in cell migration. Involved in the early stage of autophagosome formation. Modulates the intracellular level of PtdIns3P (phosphatidylinositol 3-phosphate) and activates PIK3C3 kinase activity. May act as a scaffold, independently of its lipid kinase activity to positively regulate autophagy. May have a role in insulin signaling as scaffolding protein in which the lipid kinase activity is not required. May have a kinase-independent function in regulating cell proliferation and in clathrin-mediated endocytosis. Mediator of oncogenic signal in cell lines lacking PTEN. The lipid kinase activity is necessary for its role in oncogenic transformation. Required for the growth of ERBB2 and RAS driven tumors. Also has a protein kinase activity showing autophosphorylation.

Classification

Family (Pfam)

PF00454 PI3_PI4_kinase, PF00792 PI3K_C2, PF02192 PI3K_p85B, PF00794 PI3K_rbd, PF00613 PI3Ka

InterPro

ARM-type_fold, C2_domain_sf, Kinase-like_dom_sf, PI3-kinase_beta_cat, PI3/4_kinase, PI3/4_kinase_cat_dom, PI3/4_kinase_cat_sf, PI3/4_kinase_CS, PI3K-type_C2_dom, PI3K_ABD, PI3K_accessory_dom, PI3K_accessory_sf, PI3K_Ras-bd_dom, Ubiquitin-like_domsf

Functional cluster

Zinc-Finger & Ubiquitination Proteins

Gene Ontology · 44

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0005730 nucleolus
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0005942 phosphatidylinositol 3-kinase complex
• GO:0005943 phosphatidylinositol 3-kinase complex, class IA
• GO:0005886 plasma membrane
• GO:0016303 1-phosphatidylinositol-3-kinase activity
• GO:0046934 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity
• GO:0035005 1-phosphatidylinositol-4-phosphate 3-kinase activity
• GO:0005524 ATP binding
• GO:0043560 insulin receptor substrate binding
• GO:0106310 protein serine kinase activity
• GO:0004674 protein serine/threonine kinase activity
• GO:0006914 autophagy
• GO:0016477 cell migration
• GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway
• GO:0006935 chemotaxis
• GO:0006897 endocytosis
• GO:0007186 G protein-coupled receptor signaling pathway
• GO:0042267 natural killer cell mediated cytotoxicity
• GO:1903298 negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway
• GO:0043409 negative regulation of MAPK cascade
• GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• GO:1903671 negative regulation of sprouting angiogenesis
• GO:1900747 negative regulation of vascular endothelial growth factor signaling pathway
• GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction
• GO:0046854 phosphatidylinositol phosphate biosynthetic process
• GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process
• GO:0048015 phosphatidylinositol-mediated signaling
• GO:0030168 platelet activation
• GO:0070527 platelet aggregation
• GO:0010508 positive regulation of autophagy
• GO:0010595 positive regulation of endothelial cell migration
• GO:0010628 positive regulation of gene expression
• GO:0033031 positive regulation of neutrophil apoptotic process
• GO:0045429 positive regulation of nitric oxide biosynthetic process
• GO:0035022 positive regulation of Rac protein signal transduction
• GO:0001952 regulation of cell-matrix adhesion
• GO:2000369 regulation of clathrin-dependent endocytosis
• GO:0002931 response to ischemia
• GO:0007165 signal transduction
• GO:0003376 sphingosine-1-phosphate receptor signaling pathway

Drugs targeting this protein · 28

• PF-04691502 inhibitor
• OMIPALISIB inhibitor
• IZORLISIB inhibitor
• DACTOLISIB inhibitor
• APITOLISIB inhibitor
• BUPARLISIB inhibitor
• AZD-6482 inhibitor
• RECILISIB inhibitor
• SF-1126 inhibitor
• TASELISIB inhibitor
• SAR-260301 inhibitor
• GSK-2636771 inhibitor
• PILARALISIB inhibitor
• VS-5584 inhibitor
• AZD-8186 inhibitor
• GSK-1059615 inhibitor
• BGT-226 inhibitor
• VOXTALISIB inhibitor
• FIMEPINOSTAT inhibitor
• BAY-1082439 inhibitor
• PAXALISIB inhibitor
• SONOLISIB inhibitor
• SAMOTOLISIB inhibitor
• PUQUITINIB MESYLATE DIHYDRATE inhibitor
• PANULISIB inhibitor
• PICTILISIB inhibitor
• ZSTK-474 inhibitor
• GEDATOLISIB inhibitor

Related proteins · sequence + function similarity

• Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform 0.99
• Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform 0.99
• Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 0.95
• Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 0.95
• Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 0.95
• Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 0.95
• Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform 0.92
• Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform 0.92
• Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform 0.91
• Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform 0.83
• Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform 0.80
• Phosphatidylinositol 3-kinase catalytic subunit type 3 0.75

Co-cited proteins · studied together in the literature

• Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform 1 shared papers
• Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform 2 shared papers
• Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform 2 shared papers
• Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 2 shared papers
• Forkhead box protein M1 1 shared papers
• Phosphatidylinositol 3-kinase regulatory subunit alpha 1 shared papers

Literature · 14 cited papers

• PI3K activation is enhanced by FOXM1D binding to p110 and p85 subunits. Signal Transduct. Target. Ther. · 2020
• Nuclear but not cytosolic phosphoinositide 3-kinase beta has an essential function in cell survival. Mol. Cell. Biol. · 2011
• A beta version of life: p110beta takes center stage. Oncotarget · 2010
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Regulation and roles of PI3Kbeta, a major actor in platelet signaling and functions. Adv. Enzyme Regul. · 2011
• A biochemical mechanism for the oncogenic potential of the p110beta catalytic subunit of phosphoinositide 3-kinase. Proc. Natl. Acad. Sci. U.S.A. · 2010
• p85 Associates with unphosphorylated PTEN and the PTEN-associated complex. Mol. Cell. Biol. · 2009
• PTEN-deficient cancers depend on PIK3CB. Proc. Natl. Acad. Sci. U.S.A. · 2008
• Essential roles of PI(3)K-p110beta in cell growth, metabolism and tumorigenesis. Nature · 2008
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Cloning, expression, purification, and characterization of the human Class Ia phosphoinositide 3-kinase isoforms. Protein Expr. Purif. · 2004
• Identification and characterization of the autophosphorylation sites of phosphoinositide 3-kinase isoforms beta and gamma. J. Biol. Chem. · 2003
• … and 2 more in the literature graph