{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T11:12:39Z","timestamp":1775041959343,"version":"3.50.1"},"reference-count":34,"publisher":"Rockefeller University Press","issue":"4","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,8,18]]},"abstract":"<jats:p>The cytosolic SHP-1 and transmembrane CD45 protein tyrosine phosphatases (PTP) play critical roles in regulating signal transduction via the B cell antigen receptor (BCR). These PTPs differ, however, in their effects on BCR function. For example, BCR-mediated mitogenesis is essentially ablated in mice lacking CD45 (CD45\u2212), but is enhanced in SHP-1\u2013deficient motheaten (me) and viable motheaten (mev) mice. To determine whether these PTPs act independently or coordinately in modulating the physiologic outcome of BCR engagement, we assessed B cell development and signaling in CD45-deficient mev (CD45\u2212\/SHP-1\u2212) mice. Here we report that the CD45\u2212\/SHP-1\u2212 cells undergo appropriate induction of protein kinase activity, mitogen-activated protein kinase activation, and proliferative responses after BCR aggregation. However, BCR-elicited increases in the tyrosine phosphorylation of several SHP-1\u2013associated phosphoproteins, including CD19, were substantially enhanced in CD45\u2212\/SHP-1\u2212, compared to wild-type and CD45\u2212 cells. In addition, we observed that the patterns of cell surface expression of \u03bc, \u03b4, and CD5, which distinguish the PTP-deficient from normal mice, are largely restored to normal levels in the double mutant animals. These findings indicate a critical role for the balance of SHP-1 and CD45 activities in determining the outcome of BCR stimulation and suggest that these PTPs act in a coordinate fashion to couple antigen receptor engagement to B cell activation and maturation.<\/jats:p>","DOI":"10.1084\/jem.186.4.581","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:49:30Z","timestamp":1027702170000},"page":"581-588","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":44,"title":["The Motheaten Mutation Rescues B Cell Signaling and Development in CD45-deficient Mice"],"prefix":"10.1084","volume":"186","author":[{"given":"Giovanni","family":"Pani","sequence":"first","affiliation":[{"name":"From the *Department of Immunology, \u2021Department of Medicine and Molecular and Medical Genetics, University of Toronto, \u00a7The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and \u2016The Wellesley Hospital Research Institute, Wellesley Hospital, Toronto, Ontario, M4Y 1J3, Canada"},{"name":"From the *Department of Immunology, \u2021Department of Medicine and Molecular and Medical Genetics, University of Toronto, \u00a7The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and \u2016The Wellesley Hospital Research Institute, Wellesley Hospital, Toronto, Ontario, M4Y 1J3, Canada"},{"name":"From the *Department of Immunology, \u2021Department of Medicine and Molecular and Medical Genetics, University of Toronto, \u00a7The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and \u2016The Wellesley Hospital Research Institute, Wellesley Hospital, Toronto, Ontario, M4Y 1J3, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine A.","family":"Siminovitch","sequence":"additional","affiliation":[{"name":"From the *Department of Immunology, \u2021Department of Medicine and Molecular and Medical Genetics, University of Toronto, \u00a7The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and \u2016The Wellesley Hospital Research Institute, Wellesley Hospital, Toronto, Ontario, M4Y 1J3, Canada"},{"name":"From the *Department of Immunology, \u2021Department of Medicine and Molecular and Medical Genetics, University of Toronto, \u00a7The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and \u2016The Wellesley Hospital Research Institute, Wellesley Hospital, Toronto, Ontario, M4Y 1J3, Canada"},{"name":"From the *Department of Immunology, \u2021Department of Medicine and Molecular and Medical Genetics, University of Toronto, \u00a7The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and \u2016The Wellesley Hospital Research Institute, Wellesley Hospital, Toronto, Ontario, M4Y 1J3, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher J.","family":"Paige","sequence":"additional","affiliation":[{"name":"From the *Department of Immunology, \u2021Department of Medicine and Molecular and Medical Genetics, University of Toronto, \u00a7The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and \u2016The Wellesley Hospital Research Institute, Wellesley Hospital, Toronto, Ontario, M4Y 1J3, Canada"},{"name":"From the *Department of Immunology, \u2021Department of Medicine and Molecular and Medical Genetics, University of Toronto, \u00a7The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and \u2016The Wellesley Hospital Research Institute, Wellesley Hospital, Toronto, Ontario, M4Y 1J3, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[1997,8,18]]},"reference":[{"key":"2023072507394075400_B1","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1146\/annurev.iy.12.040194.002325","article-title":"Signal transduction by the B cell antigen receptor and its coreceptors","volume":"12","author":"Cambier","year":"1994","journal-title":"Annu Rev Immunol"},{"key":"2023072507394075400_B2","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/0952-7915(94)90113-9","article-title":"Transmembrane signalling by the B cell antigen receptor","volume":"6","author":"Peaker","year":"1994","journal-title":"Curr Opin Immunol"},{"key":"2023072507394075400_B3","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/0952-7915(94)90115-5","article-title":"Role of tyrosine kinases in lymphocyte activation","volume":"6","author":"Sefton","year":"1994","journal-title":"Curr Opin Immunol"},{"key":"2023072507394075400_B4","doi-asserted-by":"crossref","first-page":"7182","DOI":"10.1073\/pnas.85.19.7182","article-title":"The leukocyte common antigen (CD45): a putative receptor-linked protein tyrosine phosphatase","volume":"85","author":"Charbonneau","year":"1988","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023072507394075400_B5","first-page":"836","article-title":"Protein-tyrosine phosphatase containing SH2 domains. 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