Epidermal Growth Factor Receptor Tyrosine Kinase Mediates Ras Activation by Gonadotropin-releasing Hormone

摘要: Abstract Gonadotropin releasing hormone (GnRH) contributes to the maintenance of gonadotrope function by increasing extracellular signal-regulated kinase (ERK) activity subsequent binding its cognate G-protein-coupled receptor. As GnRH receptor exclusively interacts with Gq/11 proteins and as expression is regulated in a β-arrestin-independent fashion, it represents good model systematically dissect underlying signaling pathways. In αT3-1 gonadotropes endogenously expressing receptor, challenge resulted rapid increase ERK which was attenuated epidermal growth factor (EGFR)-specific tyrosine inhibitor AG1478. COS-7 cells transiently human agonist-induced activation independent free Gβγ subunits but could be mimicked short-term phorbol ester treatment. Most notably, Gq/11-induced sensitive N17-Ras C-terminal Src also other dominant negative mutants components localized upstream Ras, like Shc EGFR. well esters led Ras cells, dependent on EGFR kinases, indicating that both kinases act downstream protein C (PKC) Ras. However, did not contribute phosphorylation. or PKC-dependent autophosphorylation. Furthermore, 5-min treatment sufficient trigger phosphorylation platelet-derived factor-β L cells. Thus, several cell systems PKC able stimulate via kinases.