Fig. 15.

Proposed Model for the Intracellular Mechanism of CART Action in Bovine GCs

FSH stimulates Erk1/2 and Akt activation whereas CART treatment accelerates the termination of FSH-induced Erk1/2 and Akt signaling. CART stimulation alone also induces Erk1/2 activation in bovine GCs via a G_o/i-PKC-MEK-dependent pathway. Whether the CART-induced G_o/i protein directly phosphorylates PKC, which in turn activates MEK and thus Erk1/2, or whether Erk1/2 is also activated in a PKC-independent manner is not clear. However, the CART-stimulated Erk1/2 activation is independent of PKA, PI3K, and RTK. Expression of DUSP5 is dependent on Erk1/2, thereby exhibiting a negative feedback loop in which activated Erk1/2 induces DUSP5 expression, which in turn terminates Erk1/2 activation. CART-induced DUSP5 expression is functionally required for CART-induced termination of Erk1/2 signaling and is mediated by Erk1/2- and transcription-dependent mechanisms. CART increases PP2A expression, which is also functionally required for CART-induced termination of Erk1/2 and Akt activation, and CART regulation of PP2A expression is mediated by transcription-dependent and -independent mechanisms. CART treatment also impairs the proteasomal degradation of both DUSP5 and PP2A, resulting in their accumulation. FSHR, FSH receptor.