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Suppression of growth factor-mediated MAP kinase activation by v-raf in macrophages, a putative role for the MKP-1 phosphatase

: Krautwald, S.; Dent, P.; Ruthenberg, K.; Büscher, D.; Baccarini, M.

Oncogene 10 (1995), No.6, pp.1187-1192
ISSN: 0950-9232
ISSN: 1476-5594
Journal Article
Fraunhofer ITA ( ITEM) ()
amino acid; cancer; cell line; colony stimulating factor; enzyme activation; gene expression regulation; genetic aspect; growth factor; immunology; macrophage; molecular biology; phosphorylation; protein kinase; tyrosine

Many tyrosine kinase growth factor receptors activate the MAP Kinase (MAPK) pathway by stimulating the activity of the RAF kinase. In some, but not all cell types, the expression of activated RAF is sufficient to induce constitutive MAPK activation. In BAC-1.2F5 macrophages the expression of virally activated RAF does not correlate with constitutive MAPK activation; on the contrary, growth factor-mediated stimulation of MAPK activity is suppressed in these cells. Suppression correlates with v-RAF expression, as MAPK activation is normal in a revertant cell line that stopped expressing v-RAF. Inhibition of MAPK activation is associated with lack of ERK-2 tyrosine phosphorylation, and is not due to the suppression of CSF-1-mediated MEK activation. Pretreatment with vanadate restores growth factor-stimulated activation and tyrosine phosphorylation of MAPK in v-RAF-expressing macrophages, indicating the involvement of a tyrosine phosphatase.