Abstract
Dok-R, also known as Dok-2/FRIP, belongs to the DOK family of signaling molecules that become tyrosine-phosphorylated by several different receptor and cytoplasmic tyrosine kinases. Tyrosine phosphorylation of DOK proteins establishes high affinity binding sites for other signaling molecules leading to activation of a signaling cascade. Here we show that Dok-R associates with c-Abl directly via a constitutive SH3-mediated interaction and that this binding requires a PMMP motif in the proline-rich tail of Dok-R. The Dok-R-Abl interaction is further enhanced by an active c-Abl kinase, which requires the presence of its SH2 domain. Interaction of Dok-R with c-Abl also results in an increase in c-Abl tyrosine phosphorylation and kinase activity. Furthermore, we demonstrate that this increase in kinase activity correlates with a concomitant increase in c-Abl-mediated biological activity as measured by the formation of actin microspikes. Our data are the first to demonstrate that Dok-R and c-Abl interact in both a constitutive and inducible fashion and that Dok-R influences the intracellular kinase and biological activity of c-Abl.
Original language | English (US) |
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Pages (from-to) | 30170-30179 |
Number of pages | 10 |
Journal | Journal of Biological Chemistry |
Volume | 278 |
Issue number | 32 |
DOIs | |
State | Published - Aug 8 2003 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology