Receptor-like Tyrosine Phosphatases CD45 and CD148 Have Distinct Functions in Chemoattractant-Mediated Neutrophil Migration and Response to S. aureus

SummaryNeutrophils, 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 Ca2+, 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.

Graphical AbstractFigure optionsDownload high-quality image (212 K)Download as PowerPoint slideHighlights
► RPTPs CD148 and CD45 regulate neutrophil response to S. aureus infection
► CD148 and CD45 regulate chemotaxis and GPCR-induced signaling in opposite ways
► CD148 and CD45 redundantly regulate other neutrophil functions
► CD148 and CD45 regulate GPCR pathway by preferentially targeting different SFKs