Cell transformation by v-Jun deactivates ERK MAP kinase signalling

Black, E., Walker, M., Clark, W., MacLaren, A. and Gillespie, D. (2002) Cell transformation by v-Jun deactivates ERK MAP kinase signalling. Oncogene, 21(42), pp. 6540-6548. (doi: 10.1038/sj.onc.1205851)

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Previous studies have shown that v-Jun accelerates G1 progression and enables cells to sustain S phase entry in the absence of serum growth factors. Since growth factor-dependent ERK MAP kinase signalling plays an important role in regulating the G1/S transition, we investigated whether aberrant ERK regulation might contribute to cell cycle deregulation by v-Jun. Contrary to expectation, we find that cells transformed by v-Jun exhibit a profound reduction in the basal level of active, dual-phosphorylated ERK. In addition, ERK becomes refractory to stimulation by a subset of agonists including serum, LPA, and EGF, but remains partially responsive to the phorbol ester, TPA. Biochemical analysis indicates that these defects are attributable to a combination of inefficient signal propagation between Ras and Raf within the ERK pathway and increased tonic deactivation by MAP kinase phosphatases. Taken together, these results demonstrate that cell transformation by v-Jun induces alterations in cell physiology which antagonize ERK signalling at multiple levels. The potential significance of this phenotype for oncogenesis by v-Jun is discussed.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Gillespie, Professor David
Authors: Black, E., Walker, M., Clark, W., MacLaren, A., and Gillespie, D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Oncogene

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