The rasGAP-binding protein, Dok-1, mediates activin signaling via serine/threonine kinase receptors

Norio Yamakawa, Kunihiro Tsuchida, Hiromu Sugino

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40 Citations (Scopus)

Abstract

Activins, members of the transforming growth factorβ family, are pleiotropic growth and differentiation factors. Activin A induces B-cell apoptosis. To identify the genes responsible for activin-induced apoptosis, we performed retrovirus-mediated gene trap screening in a mouse B-cell line. We identified the rasGAPbinding protein Dok-1 (p62) as an essential molecule that links activin receptors with Smad proteins. In B cells overexpressing Dok-1, activin A-induced apoptotic responses were augmented. The expression of bcl-XL was down-regulated by inhibition of the ras/Erk pathway. Activin stimulation triggered association of Dok-1 with Smad3, as well as association of Smad3 with Smad4. Dok-1 also associated with both the type I and type II activin receptors. Dok-1 has been characterized previously as a tyrosine-phosphorylated protein acting downstream of the protein tyrosine kinase pathway: intriguingly, activin signaling did not induce tyrosine phosphorylation of Dok-1. These findings indicate that Dok-1 acts as an adaptor protein that links the activin receptors with the Smads, suggesting a novel function for Dok-1 in activin signaling leading to B-cell apoptosis.

Original languageEnglish
Pages (from-to)1684-1694
Number of pages11
JournalEMBO Journal
Volume21
Issue number7
DOIs
Publication statusPublished - 02-04-2002

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All Science Journal Classification (ASJC) codes

  • Cell Biology
  • Genetics

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