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Novel p62dok family members, dok-4 and dok-5, are substrates of the c-Ret receptor tyrosine kinase and mediate neuronal differentiation

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Item Type:Article
Title:Novel p62dok family members, dok-4 and dok-5, are substrates of the c-Ret receptor tyrosine kinase and mediate neuronal differentiation
Creators Name:Grimm, J. and Sachs, M. and Britsch, S. and Di Cesare, S. and Schwarz-Romond, T. and Birchmeier, W.
Abstract:Docking proteins are substrates of tyrosine kinases and function in the recruitment and assembly of specific signal transduction molecules. Here we found that p62dok family members act as substrates for the c-Ret receptor tyrosine kinase. In addition to dok-1, dok-2, and dok-3, we identified two new family members, dok-4 and dok-5, that can directly associate with Y1062 of c-Ret. Dok-4 and dok-5 constitute a subgroup of dok family members that is coexpressed with c-Ret in various neuronal tissues. Activated c-Ret promotes neurite outgrowth of PC12 cells; for this activity, Y1062 in c-Ret is essential. c-Ret/dok fusion proteins, in which Y1062 of c-Ret is deleted and replaced by the sequences of dok-4 or dok-5, induce ligand-dependent axonal outgrowth of PC12 cells, whereas a c-Ret fusion containing dok-2 sequences does not elicit this response. Dok-4 and dok-5 do not associate with rasGAP or Nck, in contrast to p62dok and dok-2. Moreover, dok-4 and dok-5 enhance c-Ret-dependent activation of mitogen-activated protein kinase. Thus, we have identified a subclass of p62dok proteins that are putative links with downstream effectors of c-Ret in neuronal differentiation.
Keywords:Signal Transduction, Yeast Two-Hybrid System, Docking Proteins, Neural Development, Endothelia, Animals, Mice, Rats
Source:Journal of Cell Biology
ISSN:0021-9525
Publisher:Rockefeller University Press (U.S.A.)
Volume:154
Number:2
Page Range:345-354
Date:23 July 2001
Additional Information:Copyright (c) 2001 by The Rockefeller University Press
Official Publication:https://doi.org/10.1083/jcb.200102032
PubMed:View item in PubMed

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