High resolution

Module 2: Figure PtdIns 3-kinase signalling



The PtdIns 3-kinase signalling pathway.

The precursor lipid PtdIns4,5P2 is phosphorylated on the 3-position by Class I PtdIns 3-kinases (PtdIns 3-Ks) to generate the lipid second messenger PtdIns3,4,5P3. The Class 1A enzyme has regulatory subunits such as p85 that attaches the catalytic p110 subunits to the phosphorylated tyrosine residues on the cytoplasmic domains of activated growth factor receptors. The Class 1B enzymes (p110γ), which are activated by G protein-coupled receptors (GPCRs), translocate to the membrane by binding to the Gβγ subunit. When brought into the vicinity of the membrane, these PtdIns 3-kinases form the 3-phosphorylated lipid messenger PtdIns3,4,5P3, to regulate a large number of processes. It binds to other signalling components such as Btk and PLCγ (shown in pink). It stimulates phosphoinositide-dependent kinase 1/2 (PDK1/2) and protein kinase B (PKB), which activate a large number of downstream targets (yellow). It also activates monomeric G proteins (Rac, Rho and Cdc42) to stimulate both cytoskeletal rearrangement and superoxide radical (O2−•) formation (shown in green).