期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 106, 期 23, 页码 9368-9372出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0812109106
关键词
immune system; interferon gamma; lymphocyte development; protein tyrosine phosphatase
资金
- Canadian Institutes of Health Research [MOP-62887]
- National Cancer Institute of Canada [015200]
- Canadian Institutes of Health Research
- US Lymphoma Foundation
- Fonds de la recherche en sante du Quebec doctoral award
The control of tyrosine phosphorylation depends on the fine balance between kinase and phosphatase activities. Protein tyrosine phosphatase 1B (PTP-1B) and T cell protein tyrosine phosphatase (TC-PTP) are 2 closely related phosphatases known to control cytokine signaling. We studied the functional redundancy of PTP-1B and TC-PTP by deleting 1 or both copies of these genes by interbreeding TC- PTP and PTP-1B parental lines. Our results indicate that the double mutant (tcptp(-/-) ptp1b(-/-)) is lethal at day E9.5-10.5 of embryonic development with constitutive phosphorylation of Stat1. Mice heterozygous for TC- PTP on a PTP-1B-deficient background (tcptp(-/-) ptp1b(-/-)) developed signs of inflammation. Macrophages from these animals were highly sensitive to IFN-gamma, as demonstrated by increased Stat1 phosphorylation and nitric oxide production. In addition, splenic T cells demonstrated increased IFN-gamma secretion capacity. Mice with deletions of single copies of TC- PTP and PTP-1B (tcptp(+/-) ptp1b (-/-)) exhibited normal development, confirming that these genes are not interchangeable. Together, these data indicate a nonredundant role for PTP-1B and TC-PTP in the regulation of IFN signaling.
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