FigureĀ 6.
p85 roles (p110 dependent and independent) in the insulin response.
Cartoon summarising the role of the PI3K regulatory subunits in the insulin response, both in heterodimer and homodimer complexes. As part of the heterodimer, p85 mediates PI3K signalling in the insulin response and subsequent activation of the Akt/mTOR pathway, initiating glucose uptake and glycogen synthesis. Free p85 suppresses insulin signalling by competing with the p85/p110 complex and IRS-1 for pTyr binding sites on activated receptors. p85 mediated activation of JNK also suppresses signalling through IRS-1/PI3K. N-terminal mediated dimers suppress insulin signalling through activation of PTEN. SOCS-6 provides a mechanism to suppress the inhibitory actions of free p85. Insulin induced C-terminal dimers have undiscovered proliferative functions in the nucleus. Phosphorylation sites are shown as orange circles. Akt, AKR mouse thyoma; Glut4, glucose transporter 4, GSK3, glycogen synthase kinase 3, IGF-1, Insulin-like growth factor 1; IRS-1, insulin receptor substrate 1; PTEN, Phosphatase and tensin homologue; PIP2, phosphatidylinositol 4,5-biphosphate; PIP3, phosphatidylinositol (3,4,5)-trisphosphate; SOCS-6, suppressors of cytokine signalling 6.