LMP001328 UniProt Annotations
Gene Name phosphatidylinositol 3-kinase, catalytic, alpha polypeptide Protein Entry PK3CA_MOUSE UniProt ID P42337 Species Mouse
Comment type Description Catalytic Activity ATP + 1-phosphatidyl-1D-myo-inositol 4,5- bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5- trisphosphate. Catalytic Activity ATP + a protein = ADP + a phosphoprotein. Disruption Phenotype Lethal. Embryonic fibroblasts cells are resistant to oncogenic transformation induced by oncogenic receptor tyrosine kinases (RTKs), are unable to differentiate into adipocytes and deficient in cellular signaling in response to various growth factors. Defective responsiveness to insulin led to reduced somatic growth, hyperinsulinemia, glucose intolerance, hyperphagia and increased adiposity. {ECO:0000269|PubMed:16625210, ECO:0000269|PubMed:17060635, ECO:0000269|PubMed:17540175, ECO:0000269|PubMed:18449193}. Domain The PI3K-ABD domain and the PI3K-RBD domain interact with the PI3K/PI4K kinase domain. The C2 PI3K-type domain may facilitate the recruitment to the plasma membrane. The inhibitory interactions with PIK3R1 are mediated by the PI3K-ABD domain and the C2 PI3K-type domain with the iSH2 (inter-SH2) region of PIK3R1, and the C2 PI3K-type domain, the PI3K helical domain, and the PI3K/PI4K kinase domain with the nSH2 (N-terminal SH2) region of PIK3R1. {ECO:0000250}. Function Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4- phosphate) 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. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation in breast cancer cells through the PDPK1- AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. Has also serine-protein kinase activity: phosphorylates PIK3R1 (p85alpha regulatory subunit), EIF4EBP1 and HRAS. {ECO:0000269|PubMed:16625210, ECO:0000269|PubMed:16647110, ECO:0000269|PubMed:17060635, ECO:0000269|PubMed:17540175, ECO:0000269|PubMed:18449193, ECO:0000269|PubMed:21540297}. Interaction P01112:HRAS (xeno); NbExp=2; IntAct=EBI-641748, EBI-350145; P26450:Pik3r1; NbExp=6; IntAct=EBI-641748, EBI-641764; Similarity Belongs to the PI3/PI4-kinase family. {ECO:0000255|PROSITE-ProRule:PRU00877, ECO:0000255|PROSITE- ProRule:PRU00879, ECO:0000255|PROSITE-ProRule:PRU00880}. Similarity Contains 1 C2 PI3K-type domain. {ECO:0000255|PROSITE- ProRule:PRU00880}. Similarity Contains 1 PI3K-ABD domain. {ECO:0000255|PROSITE- ProRule:PRU00877}. Similarity Contains 1 PI3K/PI4K domain. {ECO:0000255|PROSITE- ProRule:PRU00269}. Similarity Contains 1 PI3K-RBD domain. {ECO:0000255|PROSITE- ProRule:PRU00879}. Similarity Contains 1 PIK helical domain. {ECO:0000255|PROSITE- ProRule:PRU00878}. Subunit Heterodimer of a catalytic subunit PIK3CA and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3). Interacts with IRS1 in nuclear extracts. Interacts with RUFY3. Interacts with RASD2. Interacts with APPL1. Interacts with HRAS and KRAS. Interaction with HRAS/KRAS is required for PI3K pathway signaling and cell proliferation stimulated by EGF and FGF2. {ECO:0000250}.
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