Signaling pathways downstream of phosphoinositide 3-kinase (PI3K) affect cell growth, cell survival, and cell movement. Activation of growth factor receptor protein tyrosine kinases results in autophosphorylation on tyrosine residues and transphosphorylation of adaptor proteins, such as GAB-1 on tyrosine. PI3K translocates to the membrane and is activated by directly binding to phosphotyrosine residues of growth factor receptors or adaptors. The lipid product of PI3K, phosphatidylinositol-3,4,5-trisphosphate (PIP3), recruits a subset of signaling proteins with pleckstrin homology (PH) domains to the membrane, where they are activated. These proteins include protein serine-threonine kinases (Akt and PDK1), protein tyrosine kinases (Tec family), exchange factors for GTP-binding proteins (Grp1 and Rac exchange factors), and adaptor proteins (GAB-1). Ultimately, these proteins initiate complex sets of events that control protein synthesis, actin polymerization, cell survival, and cell cycle entry.
L. C. Cantley, Phosphoinositide 3-Kinase Pathway. Sci. STKE (Connections Map), http://stke.sciencemag.org/cgi/cm/CMP_6557. [Canonical Pathway]
Citation for this schematic: L. C. Cantley, Schematic of PI3K Signaling. Sci. STKE (Supplement to Connections Maps), http://stke.sciencemag.org/cgi/content/full/sigtrans;CMP_6557/DC2.
Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882