The 19-amino acid insertion in the tumor-associated splice isoform Rac1b confers specific binding to p120 catenin

Lidiya Orlichenko, Rory Geyer, Masahiro Yanagisawa, Davitte Khauv, Evette S. Radisky, Panos Z. Anastasiadis, Derek C. Radisky

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

The Rac1b splice isoform contains a 19-amino acid insertion not found in Rac1; this insertion leads to decreased GTPase activity and reduced affinity for GDP, resulting in the intracellular predominance of GTP-bound Rac1b. Here, using co-precipitation and proteomic methods, we find that Rac1b does not bind to many common regulators of Rho family GTPases but that it does display enhanced binding to SmgGDS, RACK1, and p120 catenin (p120ctn), proteins involved in cell-cell adhesion, motility, and transcriptional regulation. We use molecular modeling and structure analysis approaches to determine that the interaction between Rac1b and p120ctn is dependent upon protein regions that are predicted to be unstructured in the absence of molecular complex formation, suggesting that the interaction between these two proteins involves coupled folding and binding. We also find that directed cell movement initiated by Rac1b is dependent upon p120. These results define a distinct binding functionality of Rac1b and provide insight into how the distinct phenotypic program activated by this protein may be implemented through molecular recognition of effectors distinct from those of Rac1.

Original languageEnglish (US)
Pages (from-to)19153-19161
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number25
DOIs
StatePublished - Jun 18 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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