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Journal of Cell Science, Vol 113, Issue 12 2139-2147, Copyright © 2000 by Company of Biologists
JOURNAL ARTICLES |
X Yu, S Miyamoto and E Mekada
Institute of Life Science and Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Fukuoka 839-0861, Japan.
Certain integrins including alpha 2 beta 1 and alpha 3 beta 1 localize to intercellular binding sites, and thus may participate in cell-cell interactions. We demonstrated here the physical and functional associations of integrin alpha 2 beta 1 with epidermal growth factor receptor (EGFR) at intercellular adhesion sites. Immunoprecipitation with anti-integrin alpha 2 antibodies or anti-integrin beta 1 antibody resulted in preferential coprecipitation of EGFR from A431 cell lysates, while anti-EGFR antibody coprecipitated integrin alpha 2 beta 1. Chemical crosslinking confirmed the association of integrin alpha 2 beta 1 and EGFR. Colocalization of integrin alpha 2 beta 1 and EGFR at cell-cell contact sites was observed by double immunofluorescence staining of A431 cells. EGF-induced EGFR stimulation did not affect the association of integrin alpha 2 beta 1 and EGFR. However, immunostaining with the antibody specific to activated-EGFR revealed that EGFR localized at cell-cell contact sites are phosphorylated even in serum-depleted conditions, while EGFR localized to other sites is totally dephosphorylated in the same conditions. The EGFR phosphorylation in cell-cell contact sites observed in a serum-depleted culture was abrogated with a function-blocking antibody of integrin alpha 2, but not with a non-function-blocking alpha 2 antibody or function-blocking alpha 3 antibody. Moreover, the EGFR phosphorylation in serum-depleted conditions was not observed in suspended cells, or largely abrogated in sparse cells, indicating that cell-cell adhesion is required for EGFR phosphorylation. These results indicate that integrin alpha 2 beta 1 not only physically associates with EGFR but also functions in serum-independent EGFR activation at cell-cell contact sites. The present results shed a new light on the role of intercellular integrins in cell-cell interactions.
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