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.
|Number of pages||12|
|Publication status||Published - Sep 1999|
- Cell Adhesion
- Cell Transformation, Neoplastic
- Oncogene Protein pp60(v-src)
- Proto-Oncogene Proteins
- Proto-Oncogene Proteins c-cbl
- Ubiquitin-Protein Ligases
- src-Family Kinases
Burnham, M. R., Harte, M. T., & Bouton, A. H. (1999). 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. Molecular Carcinogenesis, 26(1), 20-31.