The multidomain protooncogenic protein c-Cbl binds to tubulin and stabilizes microtubules

Anjali M. Teckchandani, Anna A. Birukova, Krisztina Tar, Alexander Dmitriyevich Verin, Alexander Y. Tsygankov

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The protooncogenic protein c-Cbl is known to regulate the actin cytoskeleton. In this study, we present results indicating that c-Cbl can also regulate the microtubular network. We have shown that c-Cbl binds to tubulin and microtubules through its tyrosine kinase binding (TKB) domain. However, the character of the interactions described in this report is novel, since the G306E mutation, which disrupts the ability of c-Cbl's TKB to bind to tyrosine-phosphorylated proteins, does not affect the observed interaction between c-Cbl and microtubules. Furthermore, overexpression of c-Cbl in human pulmonary artery endothelial cells and COS-7 cells leads to microtubule stabilization. We demonstrate that this effect of c-Cbl is mediated by TKB, and, like c-Cbl binding to microtubules, is independent of the ability of TKB to bind to tyrosine-phosphorylated proteins. Finally, we have shown that c-Cbl directly polymerizes microtubules in vitro, and that TKB is necessary and sufficient for this effect of c-Cbl. In this last phenomenon, as well as in the previous ones, the effect of TKB is not sensitive to the inactivating G306E mutation. Overall, the results presented in this report suggest a novel function for c-Cbl-microtubule binding and stabilization.

Original languageEnglish (US)
Pages (from-to)114-127
Number of pages14
JournalExperimental Cell Research
Volume306
Issue number1
DOIs
StatePublished - May 15 2005
Externally publishedYes

Keywords

  • Acetylation
  • Endothelial cells
  • Microtubules
  • Polymerization
  • Stabilization
  • Tubulin
  • c-Cbl

ASJC Scopus subject areas

  • Cell Biology

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