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The results presented here show that the absence of PTP-1B affects murine myelopoiesis by modifying the ratio of monocytes to granulocytes\n                    <jats:italic>in vivo<\/jats:italic>\n                    . This bias toward monocytic development is at least in part due to a decreased threshold of response to CSF-1, because the PTP-1B \u2212\/\u2212 bone marrow presents no abnormalities at the granulocyte\u2013monocyte progenitor level but produces significantly more monocytic colonies in the presence of CSF-1. This phenomenon is not due to an increase in receptor levels but rather to enhanced phosphorylation of the activation loop tyrosine. PTP-1B \u2212\/\u2212 cells display increased inflammatory activity\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    through the constitutive up-regulation of activation markers as well as increased sensitivity to endotoxin. Collectively, our data indicate that PTP-1B is an important modulator of myeloid differentiation and macrophage activation\n                    <jats:italic>in vivo<\/jats:italic>\n                    and provide a demonstration of a physiological role for PTP-1B in immune regulation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0508563103","type":"journal-article","created":{"date-parts":[[2006,2,13]],"date-time":"2006-02-13T20:44:07Z","timestamp":1139863447000},"page":"2776-2781","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":75,"title":["Protein tyrosine phosphatase 1B negatively regulates macrophage development through CSF-1 signaling"],"prefix":"10.1073","volume":"103","author":[{"given":"Krista M.","family":"Heinonen","sequence":"first","affiliation":[{"name":"*Division of Experimental Medicine,"},{"name":"McGill Cancer Centre, and Departments of"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Dub\u00e9","sequence":"additional","affiliation":[{"name":"McGill Cancer Centre, and Departments of"},{"name":"Biochemistry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Bourdeau","sequence":"additional","affiliation":[{"name":"*Division of Experimental Medicine,"},{"name":"McGill Cancer Centre, and Departments of"},{"name":"Biochemistry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne S.","family":"Lapp","sequence":"additional","affiliation":[{"name":"*Division of Experimental Medicine,"},{"name":"Physiology, McGill University, Montreal, QC, Canada H3G 1Y6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel L.","family":"Tremblay","sequence":"additional","affiliation":[{"name":"*Division of Experimental Medicine,"},{"name":"McGill Cancer Centre, and Departments of"},{"name":"Biochemistry and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,2,13]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90190-N"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5407.1544"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.15.5479-5489.2000"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.7.1998-2010.2002"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00148-X"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3270139"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210194200"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0304242101"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/mp.55.1.46"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00149-1"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.11.3753-3762.2003"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C100583200"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.18.8429"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.2270"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.14.7.4335-4341.1994"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205324"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.0007-1048.2001.03294.x"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.8.2948.2948"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.5.2965"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.24.14094"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.9.2846"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/35004599"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.10.010"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0320(19980615)34:3<143::AID-CYTO4>3.0.CO;2-I"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/78.1.121"},{"key":"e_1_3_3_26_2","doi-asserted-by":"crossref","first-page":"518","DOI":"10.4049\/jimmunol.139.2.518","volume":"139","author":"Stuehr D. 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