Letter abstract
Nature Cell Biology 7, 78 - 85 (2004)
Published online: 12 December 2004 | doi:10.1038/ncb1209
Negative regulation of EGFR signalling through integrin-
1
1-mediated activation of protein tyrosine phosphatase TCPTP
Elina Mattila1, Teijo Pellinen1, Jonna Nevo1, Karoliina Vuoriluoto1, Antti Arjonen1 & Johanna Ivaska1
Integrin-mediated cell adhesion regulates a multitude of cellular responses, including proliferation, survival and cross-talk between different cellular signalling pathways1. So far, integrins have been mainly shown to convey permissive signals enabling anchorage-dependent receptor tyrosine kinase signalling2, 3, 4. Here we show that a collagen-binding integrin 
1
1 functions as a negative regulator of epidermal growth factor receptor (EGFR) signalling through the activation of a protein tyrosine phosphatase. The cytoplasmic tail of 1 integrin selectively interacts with a ubiquitously expressed protein tyrosine phosphatase TCPTP (T-cell protein tyrosine phosphatase) and activates it after cell adhesion to collagen. The activation results in reduced EGFR phosphorylation after EGF stimulation. Introduction of the 1 cytoplasmic domain peptide into cells induces phosphatase activation and inhibits EGF-induced cell proliferation and anchorage-independent growth of malignant cells. These data are the first demonstration of the regulation of TCPTP activity in vivo and represent a new molecular paradigm of integrin-mediated negative regulation of receptor tyrosine kinase signalling.
- VTT Technical Research Centre of Finland, Medical Biotechnology and University of Turku Centre for Biotechnology, Turku FIN-20520, Finland.
Correspondence to: Johanna Ivaska1 e-mail: johanna.ivaska@vtt.fi
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