CROSS-LINKING OF THE SURFACE-IMMUNOGLOBULIN RECEPTOR IN B-LYMPHOCYTESINDUCES A REDISTRIBUTION OF NEUROFIBROMIN BUT NOT P120-GAP

The activation of Ras proteins is a key step in the signal transductio n pathways triggered by ligand-bound cell surface receptors. The GTPas e activating proteins (GAPs) p120-GAP and neurofibromin, the neurofibr omatosis-type 1 (NF1) gene product, are thought to play an essential r ole in the regulation of Ras activity by increasing the GTPase activit y of wild type, but not activated Ras in vitro. Both GAPs are widely e xpressed in mammalian tissues thus raising the question of whether or not they have different regulatory functions. In this study, we have a nalysed the distribution of p120-GAP and neurofibromin in splenic B ly mphocytes by immunofluorescent staining. Crosslinking of surface immun oglobulin (sig), the B-lymphocyte antigen receptor, induced the redist ribution of neurofibromin. In contrast, no apparent change in the cell ular localization of p120-GAP occurred followed the cross-linking of s ig. The redistribution of neurofibromin coincided both spatially and t emporally 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 differ entially regulated in vivo and suggest that neurofibromin is a compone nt of the signaling pathway initiated by crosslinking of B lymphocyte sig. Furthermore, our observations that cocapping neurofibromin with s ig is independent of the p21(ras) redistribution suggests that the rol e of neurofibromin in B cells is not solely related to its ability to act as a Ras regulator.