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Originally published In Press as doi:10.1074/jbc.M611330200 on April 19, 2007

J. Biol. Chem., Vol. 282, Issue 25, 18481-18496, June 22, 2007
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Necl-5/Poliovirus Receptor Interacts in cis with Integrin {alpha}Vbeta3 and Regulates Its Clustering and Focal Complex Formation*Formula

Yukiko Minami{ddagger}§, Wataru Ikeda{ddagger}, Mihoko Kajita{ddagger}, Tsutomu Fujito{ddagger}§, Hisayuki Amano{ddagger}, Yoshiyuki Tamaru{ddagger}, Kaori Kuramitsu{ddagger}, Yasuhisa Sakamoto{ddagger}, Morito Monden§, and Yoshimi Takai{ddagger}1

From the Departments of {ddagger}Molecular Biology and Biochemistry and §Surgery and Clinical Oncology, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Osaka, Japan

Integrin {alpha}vbeta3, which forms focal complexes at leading edges in moving cells, is up-regulated in cancer cells and so is implicated in their invasiveness. Necl-5, originally identified as a poliovirus receptor and also up-regulated in cancer cells, colocalizes with integrin {alpha}vbeta3 at leading edges in moving cells and enhances growth factor-induced cell movement. Here, we show that Necl-5 interacts directly, in cis, with integrin {alpha}vbeta3, and enhances integrin {alpha}vbeta3 clustering and focal complex formation at leading edges in NIH3T3 cells. The extracellular region of Necl-5, but not the cytoplasmic region, is necessary for its interaction with integrin {alpha}vbeta3; however, both regions are necessary for its action. An interaction between integrin {alpha}vbeta3 and vitronectin and PDGF-induced activation of Rac are also necessary for integrin {alpha}vbeta3 clustering. The interaction between Necl-5 and integrin {alpha}vbeta3 enhances PDGF-induced Rac activation, facilitating integrin {alpha}vbeta3 clustering presumably in a feedback amplification manner. Thus, Necl-5 has a critical role in integrin {alpha}vbeta3 clustering and focal complex formation.


Received for publication, December 11, 2006 , and in revised form, March 20, 2007.

* This work was supported by grants-in-aid for Scientific Research and for Cancer Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (2005, 2006). 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.

Formula The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1-S3.

1 To whom correspondence should be addressed: Dept. of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, Osaka 565-0871, Japan. Tel.: 81-6-6879-3410; Fax: 81-6-6879-3419; E-mail: ytakai{at}molbio.med.osaka-u.ac.jp.


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