Integrin-induced epidermal growth factor (EGF) receptor activation requires c-Src and p130Cas and leads to phosphorylation of specific EGF receptor tyrosines

Laura Moro, Laura Dolce, Sara Cabodi, Elena Bergatto, Elisabetta Boeri Erba, Monica Smeriglio, Emilia Turco, Saverio Francesco Retta, Maria Gabriella Giuffrida, Mascia Venturino, Jasminka Godovac-Zimmermann, Amedeo Conti, Erik Schaefer, Laura Beguinot, Carlo Tacchetti, Paolo Gaggini, Lorenzo Silengo, Guido Tarone, Paola Defilippi

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Abstract

Integrin-mediated cell adhesion cooperates with growth factor receptors in the control of cell proliferation, cell survival, and cell migration. One mechanism to explain these synergistic effects is the ability of integrins to induce phosphorylation of growth factor receptors, for instance the epidermal growth factor (EGF) receptor. Here we define some aspects of the molecular mechanisms regulating integrin-dependent EGF receptor phosphorylation. We show that in the early phases of cell adhesion integrins associate with EGF receptors on the cell membrane in a macromolecular complex including the adaptor protein p130Cas and the c-Src kinase, the latter being required for adhesion-dependent assembly of the macromolecular complex. We also show that the integrin cytoplasmic tail, c-Src kinase, and the p130Cas adaptor protein are required for phosphorylation of EGF receptor in response to integrin-mediated adhesion. We show that integrins induce phosphorylation of EGF receptor on tyrosine residues 845, 1068, 1086, and 1173, but not on residue 1148, a major site of phosphorylation in response to EGF. In addition we find that integrin-mediated adhesion increases the amount of EGF receptor expressed on the cell surface. Therefore these data indicate that integrin-mediated adhesion induces assembly of a macromolecular complex containing c-Src and p130Cas and leads to phosphorylation of specific EGF receptor tyrosine residues.

Original languageEnglish
Pages (from-to)9405-9414
Number of pages10
JournalJournal of Biological Chemistry
Volume277
Issue number11
DOIs
Publication statusPublished - Mar 15 2002

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ASJC Scopus subject areas

  • Biochemistry

Cite this

Moro, L., Dolce, L., Cabodi, S., Bergatto, E., Erba, E. B., Smeriglio, M., Turco, E., Retta, S. F., Giuffrida, M. G., Venturino, M., Godovac-Zimmermann, J., Conti, A., Schaefer, E., Beguinot, L., Tacchetti, C., Gaggini, P., Silengo, L., Tarone, G., & Defilippi, P. (2002). Integrin-induced epidermal growth factor (EGF) receptor activation requires c-Src and p130Cas and leads to phosphorylation of specific EGF receptor tyrosines. Journal of Biological Chemistry, 277(11), 9405-9414. https://doi.org/10.1074/jbc.M109101200