The present invention discloses a negative regulation mechanism, experimental method and application of the
Agrin-MuSK-DOK7 signaling pathway. After
Agrin stimulates myotubes to activate MuSK, MuSK promotes
phosphorylation of DOK7 Tyr106. With the help of CDH1, APC2 binds to DOK7 phosphorylated at Tyr106 and mediates ubiquitination of DOK7 Lys243 mainly in the form of K48 connection, promoting the degradation of DOK7 through the
proteasome system, and ultimately leading to downregulation of DOK7
protein level, thereby achieving negative regulation of the
Agrin-MuSK-DOK7 signaling pathway. In the present invention, APC2 CDH1 By promoting the ubiquitination and degradation of DOK7, negative regulation of the Agrin-MuSK-DOK7 signaling pathway is achieved, avoiding excessive activation of the Agrin-MuSK-DOK7 signaling pathway leading to abnormal NMJ development. The present invention provides a new theoretical basis for a deeper understanding of the
molecular mechanism of
neuromuscular junction development, and also provides new ideas for the development of treatment methods for related diseases.