The formation of acetylcholine receptor (AChR) clusters at the postsynaptic muscle membrane in response to motor innervation is a key event in the development of the neuromuscular junction. The synaptic AChR clustering process is initiated by motor axon-released agrin, which activates a tyrosine kinase-based signaling pathway to cause AChR aggregation. In cultured muscle cells, AChR clustering is elicited by diverse nonneural signals, and this process is also mediated by tyrosine kinases. Conversely, the formation of new AChR clusters induced by innervation or nonneural stimuli is unfailingly associated with the dispersal of pre-existing AChR clusters, and this process is mediated by tyrosine phosphatases. In this review, we address how local kinase activation leads to global phosphatase action in muscle. More specifically, we discuss the roles of Src kinase and the SH2 domain-containing tyrosine phosphatase Shp-2 in establishing a regenerative mechanism to propagate the AChR cluster dispersing signal extrasynaptically and in defining the boundary of cluster formation subsynaptically.

响应于运动神经支配，突触后肌膜上乙酰胆碱受体（AChR）簇的形成是神经肌肉连接发展的关键事件。突触AChR聚集过程是由运动轴突释放的凝集素启动的，该蛋白激活基于酪氨酸激酶的信号传导途径，导致AChR聚集。在培养的肌肉细胞中，AChR聚集是由多种非神经信号引起的，并且该过程也由酪氨酸激酶介导。相反，由神经支配或非神经刺激诱导的新的AChR簇的形成与先前存在的AChR簇的散布毫无关联，并且这一过程是由酪氨酸磷酸酶介导的。在这篇综述中，我们探讨了局部激酶激活如何导致肌肉中整体磷酸酶的作用。进一步来说，