Dok5 is substrate of TrkB and TrkC receptors and involved in neurotrophin induced MAPK activation

Cellular Signalling
Lei ShiXiaozhong Peng

Abstract

Tropomyosin-related kinase (Trk) family receptors are a group of high affinity receptors for neurotrophin growth factors, which have pivotal functions in many physiological processes of nervous system. Trk receptors can dimerize and autophosphorylate upon neurotrophin stimulation, then recruit multiple adaptor proteins to transduct signal. In this report, we identified Dok5, a member of Dok family, as a new substrate of TrkB/C receptors. In yeast two-hybrid assay, Dok5 can interact with intracellular domain of TrkB and TrkC receptor through its PTB domain, but not with that of TrkA receptor. The interaction was then confirmed by GST pull-down assay and Co-IP experiment. Dok5 co-localized with TrkB and TrkC in differentiated PC12 cells, providing another evidence for their interaction. By using mutational analysis, we characterized that Dok5 PTB domain bound to Trk receptor NPQY motif in a kinase-activity-dependent manner. Furthermore, competition experiment indicated that Dok5 competed with N-shc for binding to the receptors at the same site. Finally, we showed that Dok5 was involved in the activation of MAPK pathway induced by neurotrophin stimulation. Taken together, these results suggest that Dok5 acts as substrate of TrkB/C...Continue Reading

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Citations

Nov 27, 2008·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Feng ZhangCheng He
Mar 11, 2010·Journal of the American Academy of Child and Adolescent Psychiatry·Xinmin LiuFrancis J McMahon
Oct 6, 2009·Journal of Molecular and Cellular Cardiology·Jianyan WenXiaozhong Peng
Nov 17, 2009·Immunological Reviews·Ryuichi MashimaYuji Yamanashi
Aug 21, 2013·Neuroscience Letters·Yanfang PanXiaozhong Peng
May 3, 2016·International Journal of Molecular Sciences·Rabeah A Al-TemaimiFahd Al-Mulla
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Oct 24, 2018·Cancer Gene Therapy·Lin ZhangLin Fu

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