Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
The Database for Annotation, Visualization and Integrated Discovery
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phosphoinositide-3-kinase regulatory subunit 2(PIK3R2) phosphoinositide-3-kinase regulatory subunit 2(PIK3R2) Related Genes Homo sapiens
CHROMOSOME 19,
CYTOBAND 19q13.2-q13.4,
ENSEMBL_GENE_ID ENSG00000105647, ENSG00000268173,
GENERIF_SUMMARY Mutant viruses carrying NS1 with mutations in SH3 binding motif 1 failed to interact with p85ss and induce the subsequent activation of PI3K/Akt pathway., in VSMCs exposed to hyperglycemia, IGF-I stimulation of Shc facilitates the transfer of Grb2 to p85 resulting in enhanced PI3K activation and AKT phosphorylation leading to enhanced cell proliferation and migration, the influenza A virus NS1 protein interacts with the p85beta, but not the p85alpha, subunit of phosphatidylinositol 3-kinase, FGFR3 and p85 proteins interact in myeloma cells which express p85alpha and p85beta., p85alpha and p85beta may recruit proteins in the endocytic machinery on Epo stimulation; mutated EpoRs from primary familial and congenital polycythemia patients lacking the 3 important tyrosines do not bind p85 or internalize on stimulation, PTEN-p85 association involves the unphosphorylated form of PTEN engaged within the PTEN-associated complex and also includes the p110beta isoform of PI3K., Data show that mesothelin is a potential target in reducing resistance to cytotoxic drugs, and mesothelin-treated cells revealed rapid tyrosine phosphorylation of the p85 subunit of PI3K., NS5A mediates activation of beta-catenin in a phosphoinositide-3 kinase-dependent fashion., oncogenic p85 mutations lead to a loss of a C2-iSH2 domain contact that is required for inhibition of p110alpha by p85., the PTEN phosphatase is active against the PI3K p85beta subunit and dephosphorylates a protein involved in insulin signaling where known downstream consequences are increased cell migration, motility, and invasion., Macropinocytosis is regulated by interactions between Abi1 pY213 and the C-terminal SH2 domain of p85-thereby linking Abl kinase signaling to p85-dependent regulation of macropinocytosis., Overexpression of SH3 domain of p85beta inhibits influenza A virus replication., The crystal structure of human p85beta iSH2 determined to 3.3A resolution is reported., miR-126 could target both VEGFA and PIK3R2, and its expression was decreased in human breast cancer, implying that miR-126 may play a role in tumor genesis and growth by regulating the VEGF/PI3K/AKT signaling pathway, study shows that p110beta nuclear localization signal and p85beta nuclear export sequence regulate p85beta/p110beta nuclear localization, supporting the idea that nuclear, but not cytoplasmic, p110beta controls cell survival, This paper reports the first purification of a phosphoinositide 3-kinase and shows that the protein is a heterodimer of an 85 kd regulatory subunit that mediates binding to phosphorylated proteins and a 110 kd catalytic subunit., Multiple PIK3R1 and PIK3R2 mutations demonstrate gain of function, including disruption of a novel mechanism of pathway regulation wherein p85alpha dimers bind and stabilize PTEN., recombinant production, crystallization and X-ray structure determination at 2.0 A resolution of the SH3 domain of human p85beta is described, identified mutations in AKT3, PIK3R2 and PIK3CA in 11 unrelated families with megalencephaly-capillary malformation and megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndromes, p85beta phosphoinositide 3-kinase subunit regulates tumor progression, miR-126-mediated phosphoinositide-3-kinase regulation, not only fine-tunes VEGF-signaling, but it strongly enhances the activities of Ang-1 on vessel stabilization and maturation., Both alpha and beta isomers of the PI3K regulatory subunit p85 and full-length rotavirus NSP1 are important for this interaction, which results in efficient activation of the PI3K/Akt pathway during rotavirus infection., Data indicate PI3K p85 mediates the interaction of beta-catenin with NF-kappaB (p65)., FBXL2 mediates the ubiquitylation and degradation of p85beta on cell membranes., Study indicates that miR-126 is a tumor suppressor that inhibits gastric cancer cells proliferation by targeting PI3KR2, Crk and PLK2., the metastasis and angiogenesis functions of miR-126-3p were mediated by LRP6 and PIK3R2., The authors show that this potentiation involves reorganization of the natural CrkL-p85beta complex into a novel trimeric complex where influenza A virus NS1 serves as a bridging factor., The miR-126 was found to act as proliferation suppressor targeting PIK3R2 gene and reducing p85beta (a regulatory subunit of PI3K kinase) protein translation and lower AKT kinase activity., Constitutional and mosaic mutations in the PIK3R2 gene are associated with developmental brain disorders ranging from Bilateral perisylvian polymicrogyria with a normal head size to the megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome., indicated that miR-126 expression was negatively correlated with PIK3R2 mRNA expression,
OMIM_DISEASE Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1,
SP_COMMENT function: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., similarity:Belongs to the PI3K p85 subunit family., similarity:Contains 1 Rho-GAP domain., similarity:Contains 1 SH3 domain., similarity:Contains 2 SH2 domains., subunit:Heterodimer of a p110 (catalytic) and a p85 (regulatory) subunits.,