Signaling function of PSGL-1 in neutrophil: tyrosine-phosphorylation-dependent and c-Abl-involved alteration in the F-actin-based cytoskeleton.
P-selectin glycoprotein ligand-1 (PSGL-1) is the best-characterized selectin ligand that has been demonstrated to mediate leukocytes rolling on endothelium and leukocytes recruitment into inflamed tissue in vivo. In addition to its direct role in leukocyte capturing, PSGL-1 also functions as a signal-transducing receptor. The present work showed that after cross-linking of PSGL-1 with KPL1, an anti-PSGL-1 monoclonal antibody, PSGL-1 linked to the cytoskeleton and became a detergent-insoluble component in activated neutrophils. The antibody cross-linking led to the polymerization and redistribution of F-actin-based cytoskeleton, and this alteration of cytoskeleton was spatiotemporally related to the polarization of PSGL-1. PSGL-1's polarization was cytoskeleton-dependent because it was eliminated by cytochalasin B. Furthermore, the polymerization and redistribution of F-actin filaments were tyrosine-phosphorylation-dependent since the alteration of F-actin-based cytoskeleton was severely blocked by genistein, a universal tyrosine kinase inhibitor. STI571, a small molecule inhibitor for cytoplasmic tyrosine kinase c-Abl, also inhibited the alteration of F-actin-based cytoskeleton, and c-Abl was redistributed to where F-actin concentrated in the activated neutrophils. The results suggested that cross-linking of PSGL-1 induces the phosphorylation-dependent and c-Abl-involved alteration of F-actin-based cytoskeleton in neutrophils.
Ba
Xueqing
X
Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, Peoples Republic of China.
Chen
Cuixia
C
Gao
Yanguang
Y
Zeng
Xianlu
X
D000199:Actins / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D001549:Benzamides; D003432:Cross-Linking Reagents; D003599:Cytoskeleton / Q000378:metabolism*; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D000068877:Imatinib Mesylate; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism*
D000199:Actins; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D001549:Benzamides; D003432:Cross-Linking Reagents; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D010879:Piperazines; D011743:Pyrimidines; D014443:Tyrosine; D000068877:Imatinib Mesylate; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl