Separation of v-Src-induced mitogenesis and morphological transformation by inhibition of AP-1
| Autor: | Margaret C. Frame, V J Fincham, D H Crouch, K Simpson |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Leucine zipper
Mutant Stimulation Chick Embryo Biology Transfection Cell morphology Focal adhesion Animals Molecular Biology Cells Cultured Cell Size Cell Cycle Genes fos Cell Biology Cell cycle Molecular biology Cell biology DNA-Binding Proteins Transcription Factor AP-1 Genes src Cell Transformation Neoplastic Gene Expression Regulation v-Src Proto-Oncogene Proteins c-fos Research Article |
| Zdroj: | Frame, M C, Simpson, K, Fincham, V J & Crouch, D H 1994, ' Separation of v-Src-induced mitogenesis and morphological transformation by inhibition of AP-1 ', Molecular Biology of the Cell, vol. 5, no. 11, pp. 1177-84 . < http://www.ncbi.nlm.nih.gov/pmc/articles/PMC301144/ > |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.5.11.1177 |
| Popis: | v-Src activity results in both morphological transformation and reentry of quiescent chick embryo fibroblasts (CEF) into cell cycle. We have previously used temperature-sensitive v-Src mutants to show that enhanced activity of cellular AP-1 in the first few hours after activation of v-Src invariably precedes the biological consequences. Here we have investigated whether the early activation of AP-1 is essential for any or all of the v-Src responses by using a mutant c-Fos that comprises the leucine zipper and a disrupted basic region. Expression of the c-Fos mutant partially reduced cellular AP-1 activity in exponentially growing cells. However, in CEF that had been made quiescent by serum deprivation, v-Src-induced stimulation of AP-1 DNA binding activity was substantially reduced. In addition, quiescent CEF stably transfected with this mutant show an impaired mitogenic response to v-Src, indicating that the AP-1 stimulation is a necessary prerequisite for cell-cycle reentry. The ability of v-Src to morphologically transform quiescent CEF was not impaired by the inhibition of AP-1 stimulation, indicating that the mitogenic and morphological consequences of v-Src have distinguishable biochemical mediators. Focal adhesion kinase, a recently identified determinant of cell morphology, undergoes a gel mobility shift, characteristic of its hyperphosphorylated state, in response to v-Src activation in cells expressing the inhibitory AP-1 protein. This provides further evidence that the pathways that regulate morphological transformation are independent of AP-1. |
| Databáze: | OpenAIRE |
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