Leucine-zipper-mediated homo- and hetero-dimerization of GIT family p95-ARF GTPase-activating protein, PIX-, paxillin-interacting proteins 1 and 2

Simona Paris, Renato Longhi, Paolo Santambrogio, Ivan De Curtis

Research output: Contribution to journalArticle

Abstract

ADP-ribosylation factor GTPase-activating proteins (ARFGAPs) of the G-protein-coupled receptor kinase interactor 1/p95 paxillin kinase linker/p95-ARFGAP Pak-interacting exchange factor paxillin-binding protein (APP)-1 family are multidomain proteins, which interact functionally with both ARF and Rac GTPases. These proteins are involved in the dynamic reorganization of adhesion and the cytoskeleton during cell motility. Our previous work [Di Cesare, Paris, Albertinazzi, Dariozzi, Andersen, Mann, Longhi and de Curtis (2000) Nat. Cell Biol. 2, 521-530] has pointed out a role for p95-APP1 in the regulation of ARF6-mediated membrane recycling. These proteins include different domains, and are capable of interacting stably with proteins that are supposed to play a role in the regulation of actin dynamics and adhesion. They contain a coiled-coil region comprising a putative leucine zipper, predicted to be involved in dimerization. In the present study, we have investigated the possibility that these proteins form dimers. Our results show that p95-APP1 forms homodimers and may also form heterodimers with the other member of the family, p95 paxillin kinase linker/p95-APP2. Both homo- and heterodimerization are disrupted by mutation of two leucine residues in the coiled-coil region of p95-APP1. The N-terminal portion of p95-APP1, including the ARFGAP domain, three ankyrin repeats and the Pak-interacting exchange factor-binding region, are not required for dimerization. Evidence is presented for the existence of endogenous oligomeric complexes. The implication of dimerization/oligomerization in the functioning of these proteins is discussed.

Original languageEnglish
Pages (from-to)391-398
Number of pages8
JournalBiochemical Journal
Volume372
Issue number2
DOIs
Publication statusPublished - Jun 1 2003

Keywords

  • Cytoskeleton
  • Pak-interacting exchange factor
  • Rac

ASJC Scopus subject areas

  • Biochemistry

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