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Characterization of Raf-1 activation in mitosis

  1. Author:
    Laird, A. D.
    Morrison, D. K.
    Shalloway, D.

  2. Author Address

    Shalloway D Cornell Univ, Biochem Mol & Cell Biol Sect Ithaca, NY 14853 USA Cornell Univ, Biochem Mol & Cell Biol Sect Ithaca, NY 14853 USA NCI, Frederick Canc Res & Dev Ctr, ABL, Mol Basis Carcinogenesis Lab,Basic Res Program Frederick, MD 21702 USA
    1. Year: 1999
  2. Journal: Journal of Biological Chemistry
    1. 274
    2. 7
    3. Pages: 4430-4439
  4. Type of Article: Article
  1. Abstract:

    We have used site-directed mutagenesis to explore the mechanisms underlying Raf-1 activation in mitosis, and we have excluded most previously characterized activating interactions. Our results indicate that the primary locus of activation lies in the carboxyl-half of the molecule, although the extent of activation can be influenced by the amino-proximal region, particularly by the Raf-1 zinc finger, We also found that Raf-1 is hyperphosphorylated in mitosis at multiple sites within residues 283-302 and that these hyperphosphorylations are not required for activation, In addition, neither Mek1 nor Mek2 are stably activated in coordination with Raf-1 in nocodazole-arrested cells. Overall, the data suggest that the mechanism(s) responsible for activating Raf-1 during mitosis, and the subsequent downstream effects, are distinct from those involved in growth factor stimulation. [References: 82]

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