p130Cas, a Substrate Associated with v-Src and v-Crk, Localizes to Focal Adhesions and Binds to Focal Adhesion Kinase
Autor: | Mary Rose Burnham, Jeffrey D. Hildebrand, M T Harte, J T Parsons, Amy H. Bouton |
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Rok vydání: | 1996 |
Předmět: |
Integrins
Retroviridae Proteins Oncogenic PTK2 Integrin Chick Embryo In Vitro Techniques Biology Biochemistry SH3 domain Oncogene Protein pp60(v-src) src Homology Domains Focal adhesion Adapter molecule crk Cell Adhesion Animals Phosphorylation Cell adhesion Molecular Biology Cells Cultured Oncogene Protein v-crk Binding Sites Molecular Structure Retinoblastoma-Like Protein p130 Proteins Cell Biology Protein-Tyrosine Kinases Phosphoproteins Molecular biology Cell biology Crk-Associated Substrate Protein Focal Adhesion Protein-Tyrosine Kinases BCAR1 embryonic structures biology.protein biological phenomena cell phenomena and immunity Cell Adhesion Molecules |
Zdroj: | Journal of Biological Chemistry. 271:13649-13655 |
ISSN: | 0021-9258 |
DOI: | 10.1074/jbc.271.23.13649 |
Popis: | p130(Cas) (crk associated substrate) has the structural characteristics of an adapter protein, containing multiple consensus SH2 binding sites, an SH3 domain, and a proline-rich domain. The structure of p130(Cas) suggests that it may act to provide a framework for protein-protein interactions; however, as yet, its functional role in cells is unknown. In this report we show that p130(Cas) is localized to focal adhesions. We demonstrate that p130(Cas) associates both in vitro and in vivo with pp125(FAK) (focal adhesion kinase), a kinase implicated in signaling by the integrin family of cell adhesion receptors. p130(Cas) also associates with pp41/43(FRNK) (pp125(FAK)-related, non-kinase), an autonomously expressed form of pp125(FAK) composed of only the C-terminal noncatalytic domain. We show that the association of p130(Cas) with pp125(Fak) and pp41/43(FRNK) is direct, and is mediated by the binding of the SH3 domain of p130(Cas) to a proline-rich sequence present in both the C terminus of pp125(FAK) and in pp41/43(FRNK). In agreement with recent studies we show that p130(Cas) is tyrosine-phosphorylated upon integrin mediated cell adhesion. The association of p130(Cas) with pp125(FAK), a kinase which is activated upon cell adhesion, is likely to be functionally important in integrin mediated signal transduction. |
Databáze: | OpenAIRE |
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