The role of SRC-CAS interactions in cellular transformation: ectopic expression of the carboxy terminus of CAS inhibits SRC-CAS interaction but has no effect on cellular transformation.
Several lines of evidence indicate that the adapter molecule p130CAS (crk-associated substrate (CAS)) is required for src-mediated cellular transformation. CAS has been shown to be heavily tyrosine-phosphorylated in src-transformed cells, and genetic variants of src that are deficient in CAS binding are also unable to mediate cellular transformation. In this report, we investigated whether CAS phosphorylation and/or its association with src are required elements of the transformation process. Expression of the carboxy-terminal src binding domain of CAS in Rat 1 fibroblasts expressing a temperature-sensitive allele of v-src inhibited the formation of src-CAS complexes and also inhibited tyrosine phosphorylation of CAS. However, expression of this protein had no effect on morphological transformation, src-mediated actin rearrangements, or anchorage-independent growth of these cells when grown at the src-permissive temperature. Thus, the ability of activated src to mediate cellular transformation is either largely independent of endogenous CAS phosphorylation and/or its association with CAS or, alternatively, the carboxy-terminus of CAS may substitute for endogenous CAS in the process of src-mediated transformation.
Burnham
M R
MR
Department of Microbiology and Cancer Center, University of Virginia Health Science Center, Charlottesville 22908, USA.
Harte
M T
MT
Bouton
A H
AH
D000199:Actins / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*; D050721:Proto-Oncogene Proteins c-cbl; D051381:Rats; D014443:Tyrosine / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*
D000199:Actins; D011518:Proto-Oncogene Proteins; D014443:Tyrosine; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; D015688:Oncogene Protein pp60(v-src); D019061:src-Family Kinases