The identification of p130cas-binding proteins and their role in cellular transformation

M R Burnham, M T Harte, A Richardson, J T Parsons, A H Bouton

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Abstract

Adaptor proteins play an important role in signal transduction by regulating the establishment and maintenance of functionally important protein complexes. A recently described member of this group of proteins is p130cas (CAS), which contains numerous sequence motifs predicted to be involved in mediating protein-protein interactions. We propose that adaptor molecules like CAS may help determine the response of a cell to a particular signal by interacting with specific subsets of cellular proteins. To test this hypothesis, we have identified potential binding partners of CAS that may play a rote in cellular transformation by the oncoproteins v-SRC and/or v-CRK. We show that individual domains of CAS associate with specific subsets of proteins in vitro, and that many of these interactions are dependent on the state of tyrosine-phosphorylation of CAS. Sequences necessary for interacting with the focal adhesion kinase pp125FAK (FAK), v-SRC and v-CRK have been mapped to distinct regions of CAS. In addition, the identification of a number of putative CAS-binding partners that are present in crk-transformed cell extracts but undetectable in normal and src-transformed cell extracts supports a model in which unique protein complexes are formed in response to different signals.
Original languageEnglish
Pages (from-to)2467-72
Number of pages6
JournalOncogene
Volume12
Issue number11
Publication statusPublished - 06 Jun 1996

Keywords

  • Carrier Proteins
  • Cell Adhesion Molecules
  • Cellular Apoptosis Susceptibility Protein
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Glutathione Transferase
  • Phosphoproteins
  • Phosphorylation
  • Protein-Tyrosine Kinases
  • Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-crk
  • Recombinant Fusion Proteins
  • Retinoblastoma-Like Protein p130
  • Tyrosine
  • src Homology Domains

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    Burnham, M. R., Harte, M. T., Richardson, A., Parsons, J. T., & Bouton, A. H. (1996). The identification of p130cas-binding proteins and their role in cellular transformation. Oncogene, 12(11), 2467-72.