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Description

Phosphatidylinositol 3-kinase regulatory subunit alpha (UniProt: Q63787, also known as PI3-kinase regulatory subunit alpha, PI3K regulatory subunit alpha, PtdIns-3-kinase regulatory subunit alpha, Phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha, PI3-kinase subunit p85-alpha, PtdIns-3-kinase regulatory subunit p85-alpha) is encoded by the Pik3r1 gene (Gene ID: 25513) in rat. PI3K regulatory subunit alpha catalyzes the phosphorylation of PI(4,5)P2 inositol ring at the 3 position to generate PI(3,4,5)P3, a potent second messenger that mediates survival signaling and insulin action. PI3 Kinase is a heterodimeric complex composed of an 85 kDa regulatory subunit and a 110 kDa catalytic subunit. Following ligand binding to receptor and activation of receptor tyrosine kinase, the p85/p110 complex is recruited to the receptor by interaction of the SH2 domain of p85 with consensus phosphotyrosine residues on receptor tyrosine kinase. This allows the p110 catalytic subunit to come in close proximity to its lipid substrates in the cell membrane. The interaction of a receptor tyrosine kinase with the p85 subunit relieves the inhibitory effect of p85 on the p110 catalytic subunit. Activated PI 3-kinase phosphorylates phosphoinositol (PI) substrates to produce PI(3)P, PI(3,4)P2, and PI(3,4,5)P3 (PIP3). These molecules act as second messengers and recruit PI 3-kinase-dependent serine/threonine kinases (PDK1) and Akt from the cytoplasm to the plasma membrane. PI 3-kinase activity is tightly regulated in normal cells. Over-activation of this pathway can perturb the control mechanisms for cell growth and survival and contribute to metastatic competence and resistance to chemotherapy. Abnormal activation of PI 3-kinases is seen in several forms of cancer. About 30% of solid tumors contain mutations in the catalytic unit of their PI 3-kinase. PI3 kinase plays a critical role in insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Mutations in Pik3r1 gene are known to be associated with insulin resistance.