Phosphatidylinositol 3—kinase (PI3K) signaling pathway

The phosphatidylinositol 3—kinase (PI3K) signaling pathway. Activated receptor tyrosine kinases (RTKs) recruit and activate PI3K, leading to increased phosphatidylinositol-3,4,5-trisphosphate (PIP3) levels. PIP3 recruits many proteins to the membrane by binding to their pleckstrin homology (PH) domains, including the serine/threonine kinases AKT, 3-phosphoinositide-dependent kinase (PDK1), and the phosphatase PH domain and leucine rich repeat protein phosphatase (PHLPP). Membrane-bound AKT is rendered fully active through its phosphorylation by PDK1 and the rapamycin-insensitive mammalian target of rapamycin (mTOR) complex (mTORC2), and it is inactivated when dephosphorylated by PHLPP. Activated AKT may phosphorylate a range of substrates, thereby activating or inhibiting these targets and resulting in cellular growth, survival, and proliferation through various mechanisms. PI3K can also regulate downstream targets, such as RAC1/CDC42, in an AKT-independent manner. Activation of the rapamycin-sensitive mTOR complex (mTORC1) is inhibited by the tuberous sclerosis complex (TSC1 and TSC2) 1 and 2, which can be regulated by AKT as well as through PI3K-independent signaling from LKB1 and AMP-activated protein kinase (AMPK). Abbreviations: GSK, glycogen synthase kinase; NF-κB, nuclear factor—κ B; PIP2, phosphatidylinositol-4,5 bisphosphate; RAC1, Ras-related C3 botulinum toxin substrate 1.

Publication

PTEN and the PI3-Kinase Pathway in Cancer. () Nader Chalhoub, et al. Annu Rev Pathol. ;4:127-150. Figure: F2. All organisms Drosophila melanogaster Mus musculus Homo sapiens Gallus gallus Danio rerio

Disease mentions