{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:21:39Z","timestamp":1791422499258,"version":"4.3.3"},"reference-count":117,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2000,11,1]],"date-time":"2000-11-01T00:00:00Z","timestamp":973036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Neutrophils, an essential component of the innate immune system, are regulated in part by signaling pathways involving protein tyrosine phosphorylation. While protein tyrosine kinase functions in regulating neutrophil behavior have been extensively investigated, little is known about the role for specific protein tyrosine phosphatases (PTP) in modulating neutrophil signaling cascades. A key role for Src homology 2 domain-containing phosphatase 1 (SHP-1), a PTP, in neutrophil physiology is, however, implied by the overexpansion and inappropriate activation of granulocyte populations in SHP-1-deficient motheaten (me\/me) and motheaten viable (mev\/mev) mice. To directly investigate the importance of SHP-1 to phagocytic cell function, bone marrow neutrophils were isolated from both me\/me and mev\/mev mice and examined with respect to their responses to various stimuli. The results of these studies revealed that both quiescent and activated neutrophils from motheaten mice manifested enhanced tyrosine phosphorylation of cellular proteins in the 60- to 80-kDa range relative to that detected in wild-type congenic control neutrophils. Motheaten neutrophils also demonstrated increased oxidant production, surface expression of CD18, and adhesion to protein-coated plastic. Chemotaxis, however, was severely diminished in the SHP-deficient neutrophils relative to control neutrophils, which was possibly attributable to a combination of defective deadhesion and altered actin assembly. Taken together, these results indicate a significant role for SHP-1 in modulating the tyrosine phosphorylation-dependent signaling pathways that regulate neutrophil microbicidal functions.<\/jats:p>","DOI":"10.4049\/jimmunol.165.10.5847","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T23:07:29Z","timestamp":1398121649000},"page":"5847-5859","source":"Crossref","is-referenced-by-count":63,"title":["Deficiency of Src Homology 2-Containing Phosphatase 1 Results in Abnormalities in Murine Neutrophil Function: Studies in\n                    <i>Motheaten<\/i>\n                    Mice"],"prefix":"10.1093","volume":"165","author":[{"given":"Joshua","family":"Kruger","sequence":"first","affiliation":[{"name":"Division of Respirology, The Toronto General Hospital Research Institute of the University Health Network , Toronto, Ontario ,","place":["Canada"]},{"name":"Department of Medicine, University of Toronto , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey R","family":"Butler","sequence":"additional","affiliation":[{"name":"Division of Cell Biology, Research Institute, The Hospital for Sick Children , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Cherapanov","sequence":"additional","affiliation":[{"name":"Division of Respirology, The Toronto General Hospital Research Institute of the University Health Network , Toronto, Ontario ,","place":["Canada"]},{"name":"Department of Medicine, University of Toronto , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Dong","sequence":"additional","affiliation":[{"name":"Division of Respirology, The Toronto General Hospital Research Institute of the University Health Network , Toronto, Ontario ,","place":["Canada"]},{"name":"Department of Medicine, University of Toronto , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hedy","family":"Ginzberg","sequence":"additional","affiliation":[{"name":"Division of Respirology, The Toronto General Hospital Research Institute of the University Health Network , Toronto, Ontario ,","place":["Canada"]},{"name":"Department of Medicine, University of Toronto , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anand","family":"Govindarajan","sequence":"additional","affiliation":[{"name":"Division of Respirology, The Toronto General Hospital Research Institute of the University Health Network , Toronto, Ontario ,","place":["Canada"]},{"name":"Department of Medicine, University of Toronto , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Grinstein","sequence":"additional","affiliation":[{"name":"Division of Cell Biology, Research Institute, The Hospital for Sick Children , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A","family":"Siminovitch","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toronto , Toronto, Ontario ,","place":["Canada"]},{"name":"The Samuel Lunenfeld Research Institute, Mount Sinai Hospital , Toronto, Ontario ,","place":["Canada"]},{"name":"Genomic Medicine Division, University Health Network , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory P","family":"Downey","sequence":"additional","affiliation":[{"name":"Division of Respirology, The Toronto General Hospital Research Institute of the University Health Network , Toronto, Ontario ,","place":["Canada"]},{"name":"Department of Medicine, University of Toronto , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2000,11,15]]},"reference":[{"key":"2026020214141495200_R1","first-page":"274","volume-title":"J. 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