Activation of the lutropin/choriogonadotropin receptor in MA-10 cells stimulates tyrosine kinase cascades that activate ras and the extracellular signal regulated kinases ( ERK1/2).
We show that activation of the recombinant lutropin/choriogonadotropin receptor (LHR) in mouse Leydig tumor cells (MA-10 cells) leads to the tyrosine phosphorylation of Shc (Src homology and collagen homology) and the formation of complexes containing Shc and Sos (Son of sevenless), a guanine nucleotide exchange factor for Ras. Because a dominant-negative mutant of Shc inhibits the LHR- mediated activation of Ras and the phosphorylation of ERK1/2, we conclude that the LHR- mediated phosphorylation of ERK1/2 is mediated, at least partially, by the classical pathway used by growth factor receptors. We also show that the endogenous epidermal growth factor receptor ( EGFR) present in MA-10 cells is phosphorylated upon activation of the LHR. The LHR- mediated phosphorylation of the EGFR and Shc, the activation of Ras, and the phosphorylation of ERK1/2 are inhibited by expression of a dominant-negative mutant of Fyn, a member of the Src family kinases (SFKs) expressed in MA-10 cells and by PP2, a pharmacological inhibitor of the SFKs. These are also inhibited, but to a lesser extent, by AG1478, an inhibitor of the EGFR kinase. We conclude that the SFKs are responsible for the LHR- mediated phosphorylation of the EGFR and Shc, the formation of complexes containing Shc and Sos, the activation of Ras, and the phosphorylation of ERK1/2.[1]References
- Activation of the lutropin/choriogonadotropin receptor in MA-10 cells stimulates tyrosine kinase cascades that activate ras and the extracellular signal regulated kinases (ERK1/2). Shiraishi, K., Ascoli, M. Endocrinology (2006) [Pubmed]
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