Role of dynamin, Src, and Ras in the protein kinase C-mediated activation of ERK by gonadotropin-releasing hormone

G-protein-coupled receptors are a large group of integral membranal recepto rs, which in response to ligand binding initiate diverse downstream signali ng. Here we studied the gonadotropin-releasing hormone (GnRH) receptor, whi ch uses Gq for its downstream signaling. We show that extracellular signal- regulated kinase (ERK) activation is fully dependent on protein kinase C (P KC), but only partially dependent on Src, dynamin, and Ras. Receptor tyrosi ne kinases, FAK, G beta gamma, and beta -arrestin, which were implicated in some G-protein-coupled receptor signaling to MAPK cascades, do not play a role in the GnRH to ERK pathway. Our results suggest that the activation of ERK by GnRH involves two distinct signaling pathways, which converge at th e level of Raf-1. The main pathway involves a direct activation of Raf-1 by PKC, and this step is partially dependent on a second pathway consisting o f Ras activation, which occurs in a dynamin-dependent manner, downstream of Src.