Phosphatidylinositol 3-kinase cascade ; GO:0014065
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See Figure 1 in [PMID 23500680] (Regulation of angiogenesis by PI3K signaling networks).
CLASSES OF PI3K
3 classes, depending on substrate specificity:
I: PIP(4,5)P2 -> PIP(3,4,5)P3 II: PI -> PI(3)P III: PI -> PI(3)P
Class I PI3Ks most commonly pop up in signaling. They have a catalytic subunit (p110) and a regulatory subunit (p85).
ACTIVATION OF PI3K
Lie downstream of RTKs and GPCRs. Lgand-activated RTKs or GPCRs recruit the p85–p110 complex via two SH2 domains present in p85 that bind to specific phosphorylated Tyr residues (Tyr-X-X-Met motif) in activated receptors or associated adapter proteins.
DOWNSTREAM EFFECTORS OF PI3K
- AKT (PKB) (most intensively studied target of class I PI3Ks)
- adaptor proteins (GAB)
- GAPs and GEFs
AKT, which is translocated to the plasma membrane upon PtdIns(3,4,5)P3 and PtdIns(3,4)P2 production. This translocation enables phosphorylation of AKT by PDK1 (on threonine 308) and mTORC2 (on serine 473), leading to full AKT activation.
AKT then phosphorylates several downstream protein targets (e.g. eNOS, mTORC1, PFKFB2, TSC2, p21, GSK3 and FOXOs), thereby converting upstream PI3K/AKT signals into diverse cellular responses
- Where does PI3K cascade start and stop?
- If we broaden PI3K signaling to be any pathway that goes via PI3K, would ligands be annotated to 'PI3K signaling' or 'activation of PI3K signaling'. Or both? (could broaden, but still limit to INTRACELLULAR signaling that goes via PI3K).