Figure 4. Activation of intracellular signaling pathways by stimulation of CRF1 receptor.
Ligand binding to CRF1 receptor activates at least three Gα subunits (αs, αi and αq) of G-protein resulting in stimulation cAMP production by adenylate cyclase (AC) with subsequent cAMP-induced phosphorylation of CREB and activation of the cAMP-responsive element (CRE). Mobilization of calcium (Ca+2) results in activation of the calcium-responsive element (CARE). Activation of AP-1 can also trigger the mitogen-activated protein kinase (MAPK) pathway through protein kinase A (PKA). In addition, αq-mediated stimulation of phospholipase C results in IP3-driven activation of activator protein 1 (AP-1) dependent promoters. Downstream signaling from CRF1 receptor regulates expression of several genes including POMC, several interleukins, involucrine and cytokeratin 14. The phenotypic effects of stimulation include: stimulation of differentiation, steroidogenesis, melanogenesis and release of arachidonic acid. CRF inhibits cell division and regulates immune response. See text and citations within for details.