| First Author | Master Z | Year | 2003 |
| Journal | J Biol Chem | Volume | 278 |
| Issue | 32 | Pages | 30170-9 |
| PubMed ID | 12777393 | Mgi Jnum | J:230352 |
| Mgi Id | MGI:5758805 | Doi | 10.1074/jbc.M301339200 |
| Citation | Master Z, et al. (2003) Dok-R binds c-Abl and regulates Abl kinase activity and mediates cytoskeletal reorganization. J Biol Chem 278(32):30170-9 |
| abstractText | 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. |
