The identification of p130cas-binding proteins and their role in cellular transformation.
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.
Burnham
M R
MR
Department of Microbiology and Cancer Center, University of Virginia, Charlottesville 22908, USA.
Harte
M T
MT
Richardson
A
A
Parsons
J T
JT
Bouton
A H
AH
D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D029563:Cellular Apoptosis Susceptibility Protein; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D005982:Glutathione Transferase / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D050737:Proto-Oncogene Proteins c-crk; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D050717:Retinoblastoma-Like Protein p130; D014443:Tyrosine / Q000378:metabolism; D018909:src Homology Domains
D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D029563:Cellular Apoptosis Susceptibility Protein; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D011993:Recombinant Fusion Proteins; D050717:Retinoblastoma-Like Protein p130; D014443:Tyrosine; D005982:Glutathione Transferase; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases