title: Receptor-like tyrosine phosphatases CD45 and CD148 have distinct functions in chemoattractant-mediated neutrophil migration and response to S. aureus.
abstract: Neutrophils, critical innate immune effectors, use bacterial-derived chemoattractant-induced G protein-coupled receptor (GPCR) signaling for their pursuit of bacteria. Tyrosine phosphorylation pathways and receptor-like tyrosine phosphatases (RPTPs) are rarely considered in chemoattractant-mediated GPCR signaling. Here, we report that two RPTPs, CD45 and CD148, previously shown to share redundant roles in positively regulating Src family kinases (SFKs) in immunoreceptor signaling pathways in B cells and macrophages, are critical in the neutrophil response to S. aureus infection and, surprisingly, in chemoattractant-mediated chemotaxis. Remarkably, deficiency in either of these RPTPs influenced neutrophil GPCR responses in unique ways. Our results reveal that CD45 positively while CD148 positively and negatively regulate GPCR function and proximal signals including Ca(2+), phosphatidylinositol 3'OH kinase (PI3K), and phospho-extracellular regulated kinase (pERK) activity. Moreover, our results suggest that CD45 and CD148 preferentially target different SFK members (Hck and Fgr versus Lyn, respectively) to positively and negatively regulate GPCR pathways.
authors.affiliation: Department of Medicine, Howard Hughes Medical Institute, Rosalind Russell Medical Research Center for Arthritis, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Jing W
authors.initials: JW
authors.lastname: Zhu
authors.forename: Kristin
authors.initials: K
authors.lastname: Doan
authors.forename: Jason
authors.initials: J
authors.lastname: Park
authors.forename: Angela H
authors.initials: AH
authors.lastname: Chau
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Lowell
authors.forename: Arthur
authors.initials: A
authors.lastname: Weiss
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D002633:Chemotaxis / Q000235:genetics / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D013211:Staphylococcus aureus / Q000276:immunology*; D013481:Superoxides / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D043562:Receptors, G-Protein-Coupled; D013481:Superoxides; D019061:src-Family Kinases; D017493:Leukocyte Common Antigens; C098066:Ptprj protein, mouse; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3
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