Figure 2.

FSHR signaling and trafficking. Upon FSH binding, the FSHR mainly activates Gαs protein, leading to conversion of ATP to cAMP by adenylyl cyclases and activation of intracellular effector kinases, including PKA. After stimulation, GRK phosphorylates and desensitizes the FSHR. Phosphorylated FSHR recruits β-arrestin, which in turn induces its own signaling, including ERK activation, as well as receptor internalization in the endosomes. FSHR potentially activates G protein-dependent and -independent signaling from the endosomal compartment, before quickly recycling back to the plasma membrane. Effector proteins drive the cellular responses, including gene transcription, cell proliferation and differentiation. APPL1, Adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1; CREB, cAMP response element binding protein; ERK, extracellular signal-regulated kinase; FSH, Follicle-stimulating hormone; GRK, G protein-coupled receptor kinase; PKA, protein Kinase A.