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Publication : Transformation of mammalian cells by constitutively active MAP kinase kinase.

First Author  Mansour SJ Year  1994
Journal  Science Volume  265
Issue  5174 Pages  966-70
PubMed ID  8052857 Mgi Jnum  J:118714
Mgi Id  MGI:3700257 Doi  10.1126/science.8052857
Citation  Mansour SJ, et al. (1994) Transformation of mammalian cells by constitutively active MAP kinase kinase. Science 265(5174):966-70
abstractText  Mitogen-activated protein (MAP) kinase kinase (MAPKK) activates MAP kinase in a signal transduction pathway that mediates cellular responses to growth and differentiation factors. Oncogenes such as ras, src, raf, and mos have been proposed to transform cells by prolonging the activated state of MAPKK and of components downstream in the signaling pathway. To test this hypothesis, constitutively active MAPKK mutants were designed that had basal activities up to 400 times greater than that of the unphosphorylated wild-type kinase. Expression of these mutants in mammalian cells activated AP-1-regulated transcription. The cells formed transformed foci, grew efficiently in soft agar, and were highly tumorigenic in nude mice. These findings indicate that constitutive activation of MAPKK is sufficient to promote cell transformation.
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