PIK3R1

PIK3R1

A gene on chromosome 5q13.1 that encodes a regulatory subunit of phosphoinositide 3-kinase. PIK3R1 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. It is necessary for the insulin-driven increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues, and it plays an important role in signalling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. PIK3R1 also plays a role in ITGB2 signalling.
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At the molecular level, these carcinomas are characterized by high-frequency genetic alterations in the PIK3CA, PIK3R1, and PTEN genes that produce inappropriate activation of the PI3K (phosphoinositide 3-kinase) [4] pathway (28-32).
In addition to p53 alterations, human serous endometrial carcinomas also harbor frequent somatic mutations in the PPP2R1A gene (which encodes a subunit of the PP2A phosphatase) and in the PIK3CA, PIK3R1, and PTEN genes within the PI3K pathway [reviewed in (24)].
Most of the remaining significantly mutated genes (PTEN, PIK3CA, PIK3R1, ARID1A, RPL22, KRAS, CTNNB1, ATR, FGFR2, CCND1) have well-documented roles in the endometrioid subtype, as discussed earlier in this review and elsewhere (24, 65).
Sixteen significantly mutated genes were discerned in this molecular subgroup (Table 1): 9 genes previously implicated in endometrial cancer (PTEN, PIK3CA, CTNNB1, ARID1A, PIK3R1, KRAS, FGFR2, CHD4, SPOP) by us and others [(17, 18); reviewed in (24)], and 7 genes (BCOR, CSMD3, CTCF, MECOM, METTL14, SGK1, SOX17) not previously recognized to have a role in endometrial tumorigenesis.
The other significantly mutated genes in the serous-like subgroup were TP53, PIK3CA, PTEN, PIK3R1, and PPP2R1A, which have well-established roles in serous endometrial tumors [reviewed in (24) ], and FBXW7 and CHD4, which we and others previously identified as significantly mutated genes in serous endometrial carcinomas (16-18).
PIK3R1 (p85a) is somatically mutated at high frequency in primary endometrial cancer.
OncoMap Genes and Mutations (a) Gene Mutations ABL1 16 AKT1 1 AKT2 2 APC 13 BRAF 50 CDK4 1 CDKN2A 11 CSF1R 7 CTNNB1 33 EGFR 51 ERBB2 8 FGFR1 2 FGFR2 6 FGFR3 8 FLT3 9 GNA11 2 GNAQ 3 GNAS 3 HRAS 16 IDH1 3 IDH2 2 JAK2 1 JAK3 3 KIT 27 KRAS 24 MAP2K1 7 MET 6 MLH1 1 MYC 6 NPM1 3 NRAS 22 PDGFRA 20 PIK3CA 23 PIK3R1 14 PTEN 15 RB1 11 RET 14 SRC 1 STK11 12 TP53 7 VHL 7 (a) OncoMap 4 consists of 439 assays designed to interrogate 471 unique mutations in 41 cancer genes.
CE decreased the expression of further genes encoding insulin-signaling pathway proteins including GSK3B, IGF1R, IGF2R, and PIK3R1.
However, CE also decreased the expression of PIK3R1 (Fig.
cinnamon extract; DMEM, Dulbecco's modified Eagle's medium; GLUT, glucose transporter; GSK3B, glycogen synthase kinase 3 beta; GYS1, glycogen synthase 1; IGF, insulin-like growth factor; IGFR, insulin-like growth factor receptor; INS, insulin; INSR, insulin receptor; IRS, insulin receptor substrate; LEP, leptin; LEPR, leptin receptor; PIK3CB, phosphatidylinositol 3-kinase, catalytic, beta; PIK3R1, phosphatidylinositol 3-kinase, regulatory subunit 1; RPL32, ribosomal protein L32; SHC1, Src homology 2 domain-containing transforming protein 1; SOS1, Son of sevenless 1; TTP, tristetraprolin; ZFP36, zinc finger protein 36.
1] phase of factor 1 mitotic cell cycle Guanine nucleotide GNB2 signaling pathway binding protein (G protein), beta polypeptide 2 Keratin 13 KRT13 Intermediate filament Keratin 15 KRT15 Intermediate filament Laminin, alpha 3 LAMA3 Cell surface receptor Phosphoinositide- PIK3R1 Phosphatidylinositol 3-kinase, regulatory 3-kinase activity subunit, polypeptide 1 Protocadherin 1 PCDH1 Cell-cell signaling Transducin (beta)-like TBL1XR1 Regulation of 1X-linked receptor 1 transcription Vav 3 oncogene VAV3 Small GTPase-mediated signal transduction V-myc myelocytomatosis MYCL 1 Transcription factor viral oncogene homolog 1 activity Xeroderma pigmentosum, XPA Nucleotide-excision complementation group A repair [iAs.