title: Activation of p21ras by nerve growth factor in neuroblastoma cells.
abstract: Nerve growth factor (NGF) is essential for the differentiation and survival of sympathetic and sensory neurones and is thought to play a role in the differentiation of neuroblastoma. In this study we have shown NGF decreased the mRNA level of the two GTPase activating proteins neurofibromin (containing the NF1-GRD) and type 1 GAP120 in two neuroblastoma cell lines, IMR-32 and SK-N-SH. This effect was seen within 15 min exposure to NGF and was maintained up to 2 h after the addition of NGF. Treatment with NGF increased the amount of GTP bound p21ras 3-fold, within 20 min exposure. Western blot analysis showed SK-N-SH and IMR-32 cells to contain equal amounts of p21ras protein and these levels were unchanged by NGF treatment. However, NGF induced an increase in the level of neurofilament L protein, which was accompanied by an increase in neurite extension. These effects of NGF occurred in the absence of growth inhibition. In conclusion, our results demonstrate a decrease in GTPase activating proteins and activation of p21ras by NGF in IMR-32 and SK-N-SH cells, thus implicating p21ras in NGF signal transduction in neuroblastoma.
authors.affiliation: Candlelighters Children's Research Laboratory, Imperial Cancer Research Fund, Cancer Medicine Research Unit and Paediatric Oncology, St. James' University Hospital, Leeds, UK.
authors.forename: S A
authors.initials: SA
authors.lastname: Burchill
authors.forename: P A
authors.initials: PA
authors.lastname: Berry
authors.forename: I J
authors.initials: IJ
authors.lastname: Lewis
mesh_terms: D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D020690:GTPase-Activating Proteins; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009447:Neuroblastoma; D025542:Neurofibromin 1; D009474:Neurons / Q000378:metabolism*; D011506:Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D020703:ras GTPase-Activating Proteins
chemical_list: D020690:GTPase-Activating Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D025542:Neurofibromin 1; D011506:Proteins; D012333:RNA, Messenger; D020703:ras GTPase-Activating Proteins; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D016283:Proto-Oncogene Proteins p21(ras)