Interaction of the Adaptor Protein Shc and the Adhesion Molecule Cadherin*
- From the ‡Department of Biochemistry and the¶Division of Dermatology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
Abstract
In mitogenic signaling pathways, Shc participates in the growth factor activation of Ras by interacting with activated receptors and/or the Grb-2·Sos complex. Using several experimental approaches we demonstrate that Shc, through its SH2 domain, forms a complex with the cytoplasmic domain of cadherin, a transmembrane protein involved in the Ca2+-dependent regulation of cell-cell adhesion. This interaction is demonstrated in a yeast two-hybrid assay, by co-precipitation from mammalian cells, and by direct biochemical analysis in vitro. The Shc-cadherin association is phosphotyrosine-dependent and is abrogated by addition of epidermal growth factor to A-431 cells maintained in Ca2+-free medium, a condition that promotes changes in cell shape. Shc may therefore participate in the control of cell-cell adhesion as well as mitogenic signaling through Ras.
Footnotes
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↵* This work is supported by National Institutes of Health Grants CA24071 (to G. C.), HL35323 (to T. I.), CA68485 (to the Vanderbilt Cancer Center), AR41943 (to the Vanderbilt Skin Disease Center), and AR01991 and by a KAO Foundation Fellowship (to M. D.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵§ These authors contributed equally to this work.
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↵‖ To whom correspondence should be addressed. Tel.: 615-322-6678; Fax: 615-322-2931.
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↵1 The abbreviations used are: PTB, phosphotyrosine-binding; EGF, epidermal growth factor; SH2,src homology 2; HRP, horseradish peroxidase; GST, glutathione S-transferase; PAGE, polyacrylamide gel electrophoresis; PBS, phosphate-buffered saline.
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↵2 Y. Xu, D.-F. Guo, and G. Carpenter, unpublished results.
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↵3 Y. Xu and G. Carpenter, unpublished results.
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- Received January 3, 1997.
- Revision received March 5, 1997.
