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

AUTOR(ES)

Yamakawa, Norio

FONTE

Oxford University Press

RESUMO

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-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.

Documentos Relacionados

• ZIP Kinase, a Novel Serine/Threonine Kinase Which Mediates Apoptosis
• Autoregulation of the Raf-1 serine/threonine kinase
• Characterization of a Hank’s Type Serine/Threonine Kinase and Serine/Threonine Phosphoprotein Phosphatase in Pseudomonas aeruginosa
• The serine/threonine kinase cyclin G-associated kinase regulates epidermal growth factor receptor signaling
• Adenovirus E1A is associated with a serine/threonine protein kinase.