Phosphorylation of neurofibromatosis type 1 gene product (neurofibromin) by cAMP-dependent protein kinase

FEBS Lett. 1996 Mar 11;382(1-2):53-9. doi: 10.1016/0014-5793(96)00137-8.


The critical function of the neurofibromatosis type 1 (NF1) gene product (neurofibromin) is not well defined except that neurofibromin has homology with a family of the GTPase-activating proteins (GAPs). In this study, we confirmed that neurofibromin is constitutively phosphorylated and detected kinase activities which specifically phosphorylate the cysteine/serine-rich domain and the C-terminal domain of the neurofibromin in cell lysate. In vitro and in-gel kinase assays strongly indicated that cAMP-dependent protein kinase (PKA) is a candidate for the neurofibromin kinase. THe biological significance of the phosphorylation of neurofibromin is unclear at present, but we speculate that neurofibromin plays a crucial role in cellular function since it links the two major cellular pathways which are the GAP-ras and PKA-associated signals.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Cell Line, Transformed
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Fibroblasts
  • Humans
  • Molecular Sequence Data
  • Neuroblastoma
  • Neurofibromatosis 1 / metabolism*
  • Neurofibromin 1
  • Phosphoproteins / analysis
  • Phosphorylation
  • Proteins / genetics
  • Proteins / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Substrate Specificity
  • Tumor Cells, Cultured


  • Neurofibromin 1
  • Phosphoproteins
  • Proteins
  • Recombinant Fusion Proteins
  • Cyclic AMP-Dependent Protein Kinases