Dok-R binds c-Abl and regulates Abl kinase activity and mediates cytoskeletal reorganization

Zubin Master, Jennifer Tran, Aseem Bishnoi, Stephen H. Chen, John M.L. Ebos, Paul Van Slyke, Robert S. Kerbel, Daniel J. Dumont

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


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 languageEnglish (US)
Pages (from-to)30170-30179
Number of pages10
JournalJournal of Biological Chemistry
Issue number32
StatePublished - Aug 8 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Dok-R binds c-Abl and regulates Abl kinase activity and mediates cytoskeletal reorganization'. Together they form a unique fingerprint.

Cite this