Erk1/2 mftogen-activated protein kinase pathway Involves in myostatin-reguiated differentiation repression
会议名称：《中国遗传学会七届二次青年研讨会》
会议日期：2006年
学科分类：0710[理学-生物学] 07[理学] 071009[理学-细胞生物学] 09[农学] 0901[农学-作物学] 090102[农学-作物遗传育种]
摘 要：The cytokines of transforming growth factor-beta (TGF-β) and its superfamily members are potent regulators of tumorigenesis and multiple cellular events. Myostatin is a member of TGF-β superfamily and plays a negative role in the control of cell proliferation and differentiation. We now demonstrate that myostatin rapidly activated the extracellular signal-regulated Wnase (Erk)1/2 cascade in C2C12 myoblasts. A more remarkable Erk1/2 activation stimulated by myostatin was observed in differentiating than proliferating cells. The results also showed that Ras was the upstream regulator and participated in myostatin-induced Erk1/2 activation because that expression of a dominant negative Ras prevented myostatin-mediated Erk1/2 activation and proliferation Inhibition. Importantly, the myostatin-suppressed myotube fusion and differentiation marker genes expression were attenuated by blockade of Erk1/2 MAPK pathway through pre-treatment with MEK1 inhibitor PD98059, indicating that myostatin-stimulated activation of Erk1/2 negatively regulates myogenic differentiation. Activin receptor Ⅱ b (ActRⅡb) was previously suggested as the only type Ⅱ membrane receptor triggering myostatin signaling. In this study, by using synthesized siRNAs and dominant negative ActRllb, we demonstrate that myostatin failed to stimulate Erk1/2 phosphoryiation and can not inhibited myoblasts differentiation in the ActRllb knockdown C2C12 cells, indicating that ActRⅡb was required for myostatin-stimulated differentiation suppression. Altogether, our findings in this report provide the first evidence to reveal functional role of the Erk1/2 MAPK pathway in myostatin action as a negative regulator of muscle cell growth.