ShcD interacts with TrkB via its PTB and SH2 domains and regulates BDNF-induced MAPK activation.
Neurotrophins regulate many aspects of neuronal function through activation of the high affinity Trk receptors. Shc family proteins are implicated in the coupling of RTK to the Ras/mitogen-activated protein kinase signaling cascade. Here we report that the fourth Shc family member, ShcD, associates with TrkB receptor and regulates BDNF-induced MAPK activation. Yeast two-hybrid assay and Co-IP experiments demonstrate ShcD interacts with TrkB in a kinase-activity-dependent manner. Confocal analysis shows ShcD cololizes well with TrkB in transfected 293T cells. Subsequent mapping experiments and mutational analysis indicate that both PTB and SH2 domains are capable of binding to TrkB and PTB domain binds to TrkB NPQY motif. Furthermore, ShcD is involved in BDNF-induced MAPK activation. In summary, we demonstrate that ShcD is a substrate of TrkB and mediates TrkB downstream signaling pathway.
You
Yuangang
Y
Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Li
Weiqi
W
Gong
Yanhua
Y
Yin
Bin
B
Qiang
Boqin
B
Yuan
Jiangang
J
Peng
Xiaozhong
X
D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D047468:Immunoprecipitation; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D020813:Receptor, trkB / Q000378:metabolism*; D055765:Shc Signaling Adaptor Proteins / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques; D018909:src Homology Domains
D019208:Brain-Derived Neurotrophic Factor; C519335:SHC4 protein, human; D055765:Shc Signaling Adaptor Proteins; D020813:Receptor, trkB; D020928:Mitogen-Activated Protein Kinases