We have recently described a preformed multi protein complex (signalosome) associated with the GnRH receptor (GnRHR) in pituitary gonadotrope cells. This signalosome included c-Src, focal adhesion kinase (FAK), paxillin, vinculin, tubulin, caveolin-1, protein kinase C (PKC) δ, PKCε, PKCα, Ras, kinase suppressor of Ras-1 (KSR), MAPK kinase (MEK) 1/2, ERK1/2 and the GnRHR. Incubation of LβT2 gonadotrope cells with GnRH resulted in a rapid phosphorylation of caveolin-1, FAK, vinculin, and paxillin on Tyr residues by the GnRH-activated c-Src. Then, GnRH activated ERK1/2 in the complex in a c-Src-dependent manner, and the activated ERK1/2 subsequently phosphorylated FAK and paxillin. Addition of GnRH to LβT2 cells transfected with GnRHR-mCherry and ERK-GFP resulted in bleb formation, ERK accumulation in the blebs and apparent cell migration. Also, addition of GnRH to LβT2 gonadotrope cells transfected with GnRHR-mCherry and paxillin-GFP resulted in enrichment of paxillin in focal adhesions in the newly formed blebs. Moreover, caveolin-1 and vinculin, which are members of the signalosome, accumulated in the blebs. Treatment whit U0126, a MEK inhibitor, caused a decreased in bleb formation. Addition of EGF to LβT2 cell resulted in minimal bleb formation, suggesting that the bleb formation is mediated via the GnRHR. We therefore propose that the role of the signalosome is to sequester a cytosolic pool of activated ERK1/2 to phosphorylate FAK and paxillin at focal adhesions apparently to mediate gonadotropes migration