Phosphorylation of neurofibromatosis type 1 gene product (neurofibromin) by cAMP-dependent protein kinase.
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.
Izawa
I
I
Department of Neurosurgery, Kobe University School of Medicine, Kobe, Japan.
Tamaki
N
N
Saya
H
H
D001483:Base Sequence; D002461:Cell Line, Transformed; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005347:Fibroblasts; D006801:Humans; D008969:Molecular Sequence Data; D009447:Neuroblastoma; D009456:Neurofibromatosis 1 / Q000378:metabolism*; D025542:Neurofibromin 1; D010750:Phosphoproteins / Q000032:analysis; D010766:Phosphorylation; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
D025542:Neurofibromin 1; D010750:Phosphoproteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D017868:Cyclic AMP-Dependent Protein Kinases