Fig. 5.

Signaling mechanisms of melanocortin 4 receptor (MC4R). MC4R couples to Gs stimulating cAMP/PKA and to Gq activating PKC dependently from PLCβ and IP₃. It also activates ERK1/2 via Gi or through mechanisms dependent from Ca²⁺, PKA, PKC or PI3K. A PKA-dependent ERK1/2 signaling is associated with food intake suppression, whereas a PKA-independent ERK1/2 seems to decrease cell apoptosis upon neuronal damage. MC4R also inhibits JNK activity, possibly to increase insulin-stimulated glucose uptake