Protein tyrosine phosphatases PTP-1B and TC-PTP play nonredundant roles in macrophage development and IFN-gamma signaling

作者：Heinonen Krista M; Bourdeau Annie; Doody Karen M; Tremblay Michel L^*

来源：Proceedings of the National Academy of Sciences, 2009, 106(23): 9368-9372.

DOI：10.1073/pnas.0812109106

• immune system
• interferon gamma
• lymphocyte development
• protein tyrosine phosphatase

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.

• 出版日期2009-6-9