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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Adaptor Proteins, Signal Transducing*
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Adaptor Proteins, Vesicular Transport*
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Amino Acid Sequence
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Animals
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Cadherins / metabolism*
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Cell Adhesion
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Cell Size
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Enzyme Inhibitors / pharmacology
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Epidermal Growth Factor / pharmacology
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Genetic Techniques
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Mice
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Molecular Sequence Data
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Phosphorylation
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Protein Binding
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Protein Tyrosine Phosphatases / antagonists & inhibitors
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Proteins / metabolism*
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Shc Signaling Adaptor Proteins
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Signal Transduction*
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Src Homology 2 Domain-Containing, Transforming Protein 1
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Tyrosine / metabolism
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Vanadates / pharmacology
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src Homology Domains*
Substances
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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Cadherins
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Enzyme Inhibitors
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Proteins
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Shc Signaling Adaptor Proteins
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Shc1 protein, mouse
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Src Homology 2 Domain-Containing, Transforming Protein 1
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pervanadate
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Vanadates
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Tyrosine
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Epidermal Growth Factor
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Protein Tyrosine Phosphatases