Co-capping of ras proteins with surface immunoglobulins in B lymphocytes.
Cellular ras genes encode a family of membrane-associated proteins (p21ras) that bind guanine nucleotide and possess a low intrinsic GTPase activity. The p21ras proteins are ubiquitously expressed in mammalian cells and are thought to be involved in a growth-promoting signal transduction pathway; their mode of action, however, remains unknown. The ligand-induced movement of cell-surface receptors seems to be a primary event in the transduction of several extracellular signals that control cell growth and differentiation. In B lymphocytes, surface immunoglobulin receptors crosslinked by antibody or other multivalent ligands form aggregates called patches, which then collect into a single assembly, a cap, at one pole of the cell. This process constitutes the initial signal for the activation of a B cell. Here we show by immunofluorescence microscopy that p21ras co-caps with surface immunoglobulin molecules in mouse splenic B lymphocytes. In contrast, no apparent change in the distribution of p21ras occurs during the capping of concanavalin A receptors. The redistribution of p21ras is apparent at the early stages (patching) of immunoglobulin capping and is inhibited by metabolic inhibitors and the cytoskeleton-disrupting agents colchicine and cytochalasin D. The distribution of another membrane-associated guanine nucleotide-binding regulatory protein, the Gi alpha subunit, is not affected by surface immunoglobulin capping. These findings demonstrate that p21ras can migrate in a directed manner along the plasma membrane and suggest that p21ras may be a component of the signalling pathway initiated by the capping of surface immunoglobulin in B lymphocytes.
Graziadei
L
L
Cold Spring Harbor Laboratory, New York 11724.
Riabowol
K
K
Bar-Sagi
D
D
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001386:Azides / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002461:Cell Line, Transformed; D003078:Colchicine / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007152:Immunologic Capping; D051379:Mice; D008807:Mice, Inbred BALB C; D016283:Proto-Oncogene Proteins p21(ras) / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology; D015398:Signal Transduction; D019810:Sodium Azide; D013154:Spleen / Q000166:cytology
D000888:Antibodies, Anti-Idiotypic; D001386:Azides; D007140:Immunoglobulin Fab Fragments; D011947:Receptors, Antigen, B-Cell; D011961:Receptors, Fc; D003208:Concanavalin A; D015638:Cytochalasin D; D019810:Sodium Azide; D019204:GTP-Binding Proteins; D016283:Proto-Oncogene Proteins p21(ras); D003078:Colchicine