title: Crosslinking of the surface immunoglobulin receptor in B lymphocytes induces a redistribution of neurofibromin but not p120-GAP.
abstract: The activation of Ras proteins is a key step in the signal transduction pathways triggered by ligand-bound cell surface receptors. The GTPase activating proteins (GAPs) p120-GAP and neurofibromin, the neurofibromatosis-type 1 (NF1) gene product, are thought to play an essential role in the regulation of Ras activity by increasing the GTPase activity of wild type, but not activated Ras in vitro. Both GAPs are widely expressed in mammalian tissues thus raising the question of whether or not they have different regulatory functions. In this study, we have analysed the distribution of p120-GAP and neurofibromin in splenic B lymphocytes by immunofluorescent staining. Crosslinking of surface immunoglobulin (slg), the B-lymphocyte antigen receptor, induced the redistribution of neurofibromin. In contrast, no apparent change in the cellular localization of p120-GAP occurred followed the cross-linking of slg. The redistribution of neurofibromin coincided both spatially and temporally with the relocalization of crosslinked slg and was inhibited by the cytoskeletal disrupting agents colchicine and cytochalasin D. These findings indicated that neurofibromin and p120-GAP can be differentially regulated in vivo and suggest that neurofibromin is a component of the signaling pathway initiated by crosslinking of B lymphocyte slg. Furthermore, our observations that cocapping neurofibromin with slg is independent of the p21ras redistribution suggests that the role of neurofibromin in B cells is not solely related to its ability to act as a Ras regulator.
authors.affiliation: Cold Spring Harbor Laboratory, New York.
authors.forename: M J
authors.initials: MJ
authors.lastname: Boyer
authors.forename: D H
authors.initials: DH
authors.lastname: Gutmann
authors.forename: F S
authors.initials: FS
authors.lastname: Collins
authors.forename: D
authors.initials: D
authors.lastname: Bar-Sagi
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology; D003432:Cross-Linking Reagents; D015638:Cytochalasin D / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D020690:GTPase-Activating Proteins; D008148:Lovastatin / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D025542:Neurofibromin 1; D015689:Oncogene Protein p21(ras) / Q000032:analysis / Q000502:physiology; D010766:Phosphorylation; D011506:Proteins / Q000032:analysis* / Q000378:metabolism* / Q000502:physiology; D011940:Receptor Aggregation / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000032:analysis* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013154:Spleen / Q000166:cytology; D020703:ras GTPase-Activating Proteins
chemical_list: D003432:Cross-Linking Reagents; D020690:GTPase-Activating Proteins; D025542:Neurofibromin 1; D011506:Proteins; D011947:Receptors, Antigen, B-Cell; D020703:ras GTPase-Activating Proteins; D015638:Cytochalasin D; D008148:Lovastatin; D015689:Oncogene Protein p21(ras); D003078:Colchicine