The P2Y2 nucleotide receptor requires interaction with αv integrins to access and activate G12

Zhongji Liao, Cheikh I. Seye, Gary A. Weisman, Laurie Erb

Research output: Contribution to journalArticle

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Abstract

The P2Y2 nucleotide receptor (P2Y2R) interacts with αv integrins to activate Go and induce chemotaxis in human 1321N1 astrocytoma cells. In this study, it was determined that the P2Y2R also requires interaction with αv integrins to activate G12 and associated signaling pathways that control chemotaxis in 1321N1 cells. Mutation of the Arg-Gly-Asp (RGD) integrin-binding sequence in the first extracellular loop of the human P2Y2R to Arg-Gly-Glu (RGE), which prevents integrin interaction, did not inhibit Gq. or ERK1/2 signaling by the P2Y2R agonist UTP but completely inhibited activation of G12 and G12-mediated events, including Rho activation, cofflin and myosin light chain-2 phosphorylation, stress fiber formation and chemotaxis towards UTP. The involvement of G12 in all these events was verified by using a dominant negative Gα12 construct. G12 activation by the P2Y2R also was inhibited by anti-αβ5 integrin antibodies and αv integrin antisense oligonucleotides, suggesting that αv integrin activity and expression are required for the P2Y2R to activate G12. CO-immunoprecipitation experiments confirmed that Ga12 protein associates with the wild-type P2Y2R and with αv integrins but not with the RGE mutant P2Y2R or with α3 integrins. Collectively, these results suggest that αv integrin complexes provide the P2Y2R with access to G12, thereby allowing activation of this heterotrimeric G protein that controls actin cytoskeletal rearrangements required for chemotaxis.

Original languageEnglish (US)
Pages (from-to)1654-1662
Number of pages9
JournalJournal of cell science
Volume120
Issue number9
DOIs
StatePublished - May 1 2007

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Keywords

  • Cell migration
  • G
  • P2Y receptor
  • Stress fibers
  • αv integrin

ASJC Scopus subject areas

  • Cell Biology

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