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Differential regulation of Raf isozymes by growth versus differentiation inducing factors in PC12 pheochromocytoma cells
Author(s) -
Wixler Viktor,
Smola Ute,
Schuler Manuela,
Rapp Ulf
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(96)00363-8
Subject(s) - isozyme , differential (mechanical device) , pheochromocytoma , chemistry , differential effects , microbiology and biotechnology , endocrinology , medicine , biology , biochemistry , enzyme , physics , thermodynamics
PC12 pheochromocytoma cells possess four known MEK activators: A‐, B‐, c‐Raf‐1 and MEKK. In order to examine whether differentiation factors or growth factors have a Raf isozyme preference for activation of the mitogenic cytoplasmic Raf‐MEK‐MAPK protein kinase cascade, the activation kinetics of these enzymes in response to epidermal growth factor (EGF) and nerve growth factor (NGF) were compared. An initial activation of all three Raf kinases was noticed, but only A‐ and B‐Raf showed sustained activation by NGF, which was not seen after EGF treatment. Furthermore, expression of oncogenic versions of all three Raf kinases as well as a potentially Raf‐independent MEK activator, v‐Mos, leads to activation of MAPK and to differentiation of PC12 cells. These data suggest a differential regulation of Raf kinases and that probably no alternative Raf substrates are involved in differentiation processes of PC12 cells.