{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T03:32:17Z","timestamp":1768620737508,"version":"3.49.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2001,6,1]],"date-time":"2001-06-01T00:00:00Z","timestamp":991353600000},"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":[[2001,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Unraveling the molecular mechanisms by which filarial nematodes, major human pathogens in the tropics, evade the host immune system remains an elusive goal. We have previously shown that excretory-secretory product-62 (ES-62), a homologue of phosphorylcholine-containing molecules that are secreted by human parasites and which is active in rodent models of filarial infection, is able to polyclonally activate certain protein tyrosine kinase and mitogen-activating protein kinase signal transduction elements in B lymphocytes. Such activation mediates desensitization of subsequent B cell Ag receptor (BCR) ligation-induced activation of extracellular signal-regulated kinase-mitogen-activated protein (ErkMAP) kinase and ultimately B cell proliferation. We now show that the desensitization is due to ES-62 targeting two major regulatory sites of B cell activation. Firstly, pre-exposure to ES-62 primes subsequent BCR-mediated recruitment of SHP-1 tyrosine phosphatase to abolish recruitment of the RasErkMAP kinase cascade via the Ig\u03b1\u03b2-ShcGrb2Sos adaptor complex interactions. Secondly, any ongoing ErkMAP kinase signaling in ES-62-primed B cells is terminated by the MAP kinase phosphatase, Pac-1 that is activated consequently to challenge via the BCR.<\/jats:p>","DOI":"10.4049\/jimmunol.166.12.7462","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T23:36:18Z","timestamp":1398036978000},"page":"7462-7468","source":"Crossref","is-referenced-by-count":37,"title":["A Filarial Nematode-Secreted Phosphorylcholine-Containing Glycoprotein Uncouples the B Cell Antigen Receptor from Extracellular Signal-Regulated Kinase-Mitogen-Activated Protein Kinase by Promoting the Surface Ig-Mediated Recruitment of Src Homology 2 Domain-Containing Tyrosine Phosphatase-1 and Pac-1 Mitogen-Activated Kinase-Phosphatase"],"prefix":"10.1093","volume":"166","author":[{"given":"Maureen R","family":"Deehan","sequence":"first","affiliation":[{"name":"Department of Immunology, University of Glasgow , Glasgow ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Harnett","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Strathclyde , Glasgow ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret M","family":"Harnett","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Glasgow , Glasgow ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2001,6,15]]},"reference":[{"key":"2025032907395234100_R1","volume-title":"Filariasis","year":"1987"},{"key":"2025032907395234100_R2","first-page":"207","volume-title":"Perspectives in Nematode Physiology and Biochemistry","year":"1995"},{"key":"2025032907395234100_R3","first-page":"241","volume-title":"Parasite Immunol.","year":"1998"},{"key":"2025032907395234100_R4","first-page":"125","volume-title":"Immunol. 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