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

Citation
J. Grimm et al., Novel p62dok family members, dok-4 and dok-5, are substrates of the c-Ret receptor tyrosine kinase and mediate neuronal differentiation, J CELL BIOL, 154(2), 2001, pp. 345-354
Citations number
64
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELL BIOLOGY
ISSN journal
0021-9525 → ACNP
Volume
154
Issue
2
Year of publication
2001
Pages
345 - 354
Database
ISI
SICI code
0021-9525(20010723)154:2<345:NPFMDA>2.0.ZU;2-S
Abstract
Docking proteins are substrates of tyrosine kinases and function in the rec ruitment and assembly of specific signal transduction molecules. Here we fo und that p62dok family members act as substrates for the c-Ret receptor tyr osine 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 promot es neurite outgrowth of PC12 cells; for this activity, Y1062 in c-Ret is es sential. 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 cel Is, whereas a c-Ret fusion containing dok-2 sequence s does not elicit this response. Dok-4 and dok-5 do not associate with rasG AP or Nck, in contrast to p62dok and dok-2. Moreover, dok-4 and dok-5 enhan ce 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.