Signaling complexes for postsynaptic differentiation.
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.
Luo
Zhenge
Z
Departments of Neurobiology, Pathology, and Physical Medicine and Rehabilitation, Civitan International Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Wang
Qiang
Q
Dobbins
G Clement
GC
Levy
Shoshanah
S
Xiong
Wen C
WC
Mei
Lin
L
D000818:Animals; D006801:Humans; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
D011950:Receptors, Cholinergic; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases