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 language | English |
|---|---|
| Pages (from-to) | 1684-1694 |
| Number of pages | 11 |
| Journal | EMBO Journal |
| Volume | 21 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 02-04-2002 |
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All Science Journal Classification (ASJC) codes
- Cell Biology
- Genetics
Cite this
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The rasGAP-binding protein, Dok-1, mediates activin signaling via serine/threonine kinase receptors. / Yamakawa, Norio; Tsuchida, Kunihiro; Sugino, Hiromu.
In: EMBO Journal, Vol. 21, No. 7, 02.04.2002, p. 1684-1694.Research output: Contribution to journal › Article
TY - JOUR
T1 - The rasGAP-binding protein, Dok-1, mediates activin signaling via serine/threonine kinase receptors
AU - Yamakawa, Norio
AU - Tsuchida, Kunihiro
AU - Sugino, Hiromu
PY - 2002/4/2
Y1 - 2002/4/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0037007204&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037007204&partnerID=8YFLogxK
U2 - 10.1093/emboj/21.7.1684
DO - 10.1093/emboj/21.7.1684
M3 - Article
C2 - 11927552
AN - SCOPUS:0037007204
VL - 21
SP - 1684
EP - 1694
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 7
ER -