L-selectin regulates actin polymerisation via activation of the small G-protein Rac2.
L-selectin mediated adhesion to endothelial cells is a crucial step in the immune response to pathogens (1, 2) and in lymphocyte homing (3, 4). Selectin molecules mediate leukocyte rolling on endothelial cells, the initial step of adhesion (5, 6). We have previously shown that stimulation of Jurkat T-lymphocytes via L-selectin results in activation of the p21Ras pathway and synthesis of reactive oxygen intermediates (7). Here, we show that cellular stimulation via L-selectin induces a change of cytoskeleton organisation demonstrated by a tenfold increase of actin filament polymerisation. This actin polymerisation is mediated by a Ras and Rac2 regulated pathway, since inhibition of Ras by transient transfection of transdominant inhibitory N17Ras or suppression of Rac2 protein expression by antisense oligonucleotides prevents L-selectin triggered actin polymerisation. Our results point to a signaling cascade from L-selectin via Ras and Rac2 to actin filaments, which might be important for leukocyte adhesion.
Brenner
B
B
Department of Pediatrics, University of Heidelberg, Germany.
Gulbins
E
E
Busch
G L
GL
Koppenhoefer
U
U
Lang
F
F
Linderkamp
O
O
D008841:Actin Cytoskeleton / Q000648:ultrastructure*; D000199:Actins / Q000378:metabolism*; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D019041:L-Selectin / Q000378:metabolism*; D011108:Polymers; D011485:Protein Binding; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D020744:rac GTP-Binding Proteins
D000199:Actins; D011108:Polymers; D019041:L-Selectin; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D020744:rac GTP-Binding Proteins