Mechanism of cAMP inhibition of MAPK activity

Schematic diagram of the mechanism of cAMP inhibition of MAPK activity. Upon stimulation in lacrimal gland acini, both VIP and the cholinergic agonist acetylcholine are released from parasympathetic nerves, which bind to their receptors and stimulate secretion by increasing [Ca2+]i and activity of PKC. The VIP receptor activates adenylate cyclase (AC) through the G protein Gαs to increase intracellular [cAMP]. cAMP, in turn, stimulates PKA activity, which leads to protein secretion. cAMP is quickly broken down to AMP by phosphodiesterase (PDE). After binding to their receptors, cholinergic agonists activate the tyrosine kinases Pyk2 and Src to stimulate the kinase cascade of Ras, Raf-1, MEK, and MAPK. EGF also activates this cascade in a similar manner. Activation of MAPK attenuates protein secretion. In addition to stimulating protein secretion, PKA inhibits Raf-1 activity, which, in turn, decreases the activity of MEK and MAPK, relieving the inhibition of secretion by MAPK and thereby potentiating secretion.

Publication

Identification of the Raf-1 Signaling Pathway Used by cAMP to Inhibit p42/p44 MAPK in Rat Lacrimal Gland Acini: Role in Potentiation of Protein Secretion. (2010) Chika Funaki, et al. Invest Ophthalmol Vis Sci. 2010 Dec;51(12):6321-6328. Figure: F8. All organisms Drosophila melanogaster Homo sapiens

Disease mentions