Luo Zhenge, Wang Qiang, Dobbins G Clement, Levy Shoshanah, Xiong Wen C, Mei Lin
Departments of Neurobiology, Pathology, and Physical Medicine and Rehabilitation, Civitan International Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
J Neurocytol. 2003 Jun-Sep;32(5-8):697-708. doi: 10.1023/B:NEUR.0000020618.65271.63.
The receptor tyrosine kinase MuSK is activated by agrin, an extracellular matrix protein believed to be utilized by motoneurons to regulate the formation or maintenance of the neuromuscular junction (NMJ). Recent studies have shed light on intracellular signaling mechanisms downstream of MuSK. Agrin enhances the activity of Rho GTPases and PAK, which is required for AChR clustering. Activation of these enzymes requires not only the kinase activity of MuSK, but also its interaction with proteins such as Dishevelled. These results suggest that MuSK may function as a scaffold tyrosine kinase that forms a multi-molecule complex for AChR clustering.
受体酪氨酸激酶肌肉特异性激酶（MuSK）由聚集蛋白激活，聚集蛋白是一种细胞外基质蛋白，运动神经元利用它来调节神经肌肉接头（NMJ）的形成或维持。最近的研究揭示了MuSK下游的细胞内信号传导机制。聚集蛋白增强了Rho GTP酶和p21激活激酶（PAK）的活性，这是乙酰胆碱受体（AChR）聚集所必需的。这些酶的激活不仅需要MuSK的激酶活性，还需要它与诸如散乱蛋白等蛋白质的相互作用。这些结果表明，MuSK可能作为一种支架酪氨酸激酶发挥作用，形成一个用于AChR聚集的多分子复合物。
