Phosphorylation by PKA of a site unique to B-Raf kinase

C R Acad Sci III. 2001 Aug;324(8):673-81. doi: 10.1016/s0764-4469(01)01356-7.

Abstract

The Raf kinases serve as central intermediates to relay signals from Ras to ERK. Cell-specific effects of these signals on growth, differentiation and survival can be observed due to the recruitment of different isoenzymes of the Raf family. The in vitro phosphorylation of a site unique to B-Raf (Ser429) has been proposed to be responsible for the negative regulation of the isoenzyme by Akt. Using phosphopetide mapping and site-directed mutagenesis we showed that Ser429 is phosphorylated upon cAMP elevation in PC12 cells and proposed that PKA is a major kinase phosphorylating the B-Raf-specific site in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • COS Cells
  • Chromatography, High Pressure Liquid
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Glutathione Transferase / genetics
  • Isoenzymes / chemistry*
  • Isoquinolines / pharmacology
  • Mutagenesis, Site-Directed
  • PC12 Cells
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Peptide Mapping
  • Phosphorylation
  • Phosphoserine / metabolism
  • Proto-Oncogene Proteins c-raf / chemistry*
  • Proto-Oncogene Proteins c-raf / genetics
  • Proto-Oncogene Proteins c-raf / metabolism*
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Sulfonamides*
  • Trypsin

Substances

  • Enzyme Inhibitors
  • Isoenzymes
  • Isoquinolines
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • Sulfonamides
  • Phosphoserine
  • Colforsin
  • Cyclic AMP
  • Glutathione Transferase
  • Proto-Oncogene Proteins c-raf
  • Cyclic AMP-Dependent Protein Kinases
  • Trypsin
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide