Multiple domains of Ruk/CIN85/SETA/CD2BP3 are involved in interaction with p85α regulatory subunit of PI 3-kinase

Emma B. Borthwick, Igor V. Korobko, Courtney Luke, Victor R. Drel, Yaroslav Ya Fedyshyn, Natalia Ninkina, Ludmila B. Drobot, Vladimir L. Buchman

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Ruk/CIN85/SETA/CD2BP3 and CD2AP/CMS/METS-1 comprise a new family of proteins involved in such fundamental processes as clustering of receptors and rearrangement of the cytoskeleton in regions of specialised cell-cell contacts, ligand-activated internalisation and targeting to lysosome degradation pathway of receptor tyrosine kinases, and apoptotic cell death. As typical adapter proteins they execute these functions by interacting with other signalling molecules via multiple protein-protein interaction interfaces: SH3 domains, Pro-rich region and coiled-coil domain. It has been previously demonstrated that Ruk is able to interact with the p85α regulatory subunit of PI 3-kinase and that the SH3 domain of p85α is required for this interaction. However, later observations hinted at a more complex mechanism than simple one-way SH3-Pro-rich interaction. Because interaction with p85α was suggested to be important for pro-apoptotic activity of the long isoform of Ruk, Ruk l/CIN85, we carried out detailed studies of the mechanism of this interaction and demonstrated that multiple domains are involved; SH3 domains of Ruk are required and sufficient for efficient interaction with full-length p85α but the SH3 domain of p85α is vital for their "activation" by ousting them from intramolecular interaction with the Pro-rich region of Ruk. Our data also suggest that homodimerisation via C-terminal coiled-coil domain affects both intra- and intermolecular interactions of Ruk proteins.

Original languageEnglish (US)
Pages (from-to)1135-1146
Number of pages12
JournalJournal of Molecular Biology
Volume343
Issue number4
DOIs
StatePublished - Oct 29 2004
Externally publishedYes

Keywords

  • adaptor protein
  • phosphatidylinositol 3-kinase
  • proline-rich region
  • protein-protein interaction
  • SH3 domain

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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