HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 47, 39050-39057, November 25, 2005

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 280/47/39050    most recent M504819200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bagchi, S. Articles by Erb, L. Search for Related Content PubMed PubMed Citation Articles by Bagchi, S. Articles by Erb, L. Social Bookmarking                      What's this?

The P2Y₂ Nucleotide Receptor Interacts with _v Integrins to Activate G_o and Induce Cell Migration^*

Sriparna Bagchi, Zhongji Liao, Fernando A. Gonzalez, Nataliya E. Chorna, Cheikh I. Seye, Gary A. Weisman, and Laurie Erb1

From the Department of Biochemistry, University of Missouri, Columbia, Missouri 65211 and Department of Chemistry, University of Puerto Rico, Rio Piedras, Puerto Rico 00931

Extracellular ATP and UTP induce chemotaxis, or directed cell migration, by stimulating the G protein-coupled P2Y₂ nucleotide receptor (P2Y₂R). Previously, we found that an arginine-glycine-aspartic acid (RGD) integrin binding domain in the P2Y₂R enables this receptor to interact selectively with _v3 and _V5 integrins, an interaction that is prevented by mutation of the RGD sequence to arginine-glycine-glutamic acid (RGE) (Erb, L., Liu, J., Ockerhausen, J., Kong, Q., Garrad, R. C., Griffin, K., Neal, C., Krugh, B., Santiago-Perez, L. I., Gonzalez, F. A., Gresham, H. D., Turner, J. T., and Weisman, G. A. (2001) J. Cell Biol. 153, 491–501). This RGD domain also was found to be necessary for coupling the P2Y₂R to G_o- but not G_q-mediated intracellular calcium mobilization, leading us to investigate the role of P2Y₂R interaction with integrins in nucleotide-induced chemotaxis. Here we show that mutation of the RGD sequence to RGE in the human P2Y₂R expressed in 1321N1 astrocytoma cells completely prevented UTP-induced chemotaxis as well as activation of G_o, Rac, and Vav2, a guanine nucleotide exchange factor for Rac. UTP also increased expression of vitronectin, an extracellular matrix protein that is a ligand for _v3/₅ integrins, in cells expressing the wild-type but not the RGE mutant P2Y₂R. P2Y₂R-mediated chemotaxis, Rac and Vav2 activation, and vitronectin up-regulation were inhibited by pretreatment of the cells with anti-_v5 integrin antibodies, _v integrin antisense oligonucleotides, or the G_i/o inhibitor, pertussis toxin. Thus, the RGD-dependent interaction between the P2Y₂R and _v integrins is necessary for the P2Y₂R to activate G_o and to initiate G_o-mediated signaling events leading to chemotaxis.

Received for publication, May 2, 2005 , and in revised form, August 31, 2005.

^* This work was supported by National Institutes of Health Grants AG18357, DE07389, and RR15565 and the F21C program of the University of Missouri-Columbia. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1 and S2.

¹ To whom correspondence should be addressed: University of Missouri-Columbia, 540F Life Sciences Center, 1201 Rollins Rd., Columbia, MO 65211. Tel.: 573-884-2065; Fax: 573-884-2537; E-mail: erbl{at}missouri.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				N. Yu, L. Erb, R. Shivaji, G. A. Weisman, and C. I. Seye Binding of the P2Y2 Nucleotide Receptor to Filamin A Regulates Migration of Vascular Smooth Muscle Cells Circ. Res., March 14, 2008; 102(5): 581 - 588. [Abstract] [Full Text] [PDF]

				J. Shen and P. E. DiCorleto ADP Stimulates Human Endothelial Cell Migration via P2Y1 Nucleotide Receptor-Mediated Mitogen-Activated Protein Kinase Pathways Circ. Res., February 29, 2008; 102(4): 448 - 456. [Abstract] [Full Text] [PDF]

				S. Taboubi, J. Milanini, E. Delamarre, F. Parat, F. Garrouste, G. Pommier, J. Takasaki, J.-C. Hubaud, H. Kovacic, and M. Lehmann G{alpha}(q/11)-coupled P2Y2 nucleotide receptor inhibits human keratinocyte spreading and migration FASEB J, December 1, 2007; 21(14): 4047 - 4058. [Abstract] [Full Text] [PDF]

				L. Stokes and A. Surprenant Purinergic P2Y2 Receptors Induce Increased MCP-1/CCL2 Synthesis and Release from Rat Alveolar and Peritoneal Macrophages J. Immunol., November 1, 2007; 179(9): 6016 - 6023. [Abstract] [Full Text] [PDF]

				Z. Liao, C. I. Seye, G. A. Weisman, and L. Erb The P2Y2 nucleotide receptor requires interaction with {alpha}v integrins to access and activate G12 J. Cell Sci., May 1, 2007; 120(9): 1654 - 1662. [Abstract] [Full Text] [PDF]