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The rasGAP‐binding protein, Dok‐1, mediates activin signaling via serine/threonine kinase receptors
Author(s) -
Yamakawa Norio,
Tsuchida Kunihiro,
Sugino Hiromu
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/21.7.1684
Subject(s) - enzyme , threonine , serine , receptor , biology , library science , genetics , computer science , biochemistry
Activins, members of the transforming growth factor‐β 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 rasGAP‐binding 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‐X L 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.