Protein tyrosine phosphatase 1B negatively regulates macrophage development through CSF-1 signaling
| Autor: | Nadia Dubé, Michel L. Tremblay, Krista M. Heinonen, Wayne S. Lapp, Annie Bourdeau |
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| Rok vydání: | 2006 |
| Předmět: |
Lipopolysaccharides
Macrophage colony-stimulating factor animal structures Myeloid Phosphatase Receptor Macrophage Colony-Stimulating Factor Protein tyrosine phosphatase Biology environment and public health Monocytes Mice medicine Animals Phosphorylation Tyrosine Protein Tyrosine Phosphatase Non-Receptor Type 1 Multidisciplinary Macrophage Colony-Stimulating Factor Macrophages Biological Sciences Macrophage Activation Mice Mutant Strains Cell biology enzymes and coenzymes (carbohydrates) medicine.anatomical_structure Tyrosine kinase 2 Cancer research Myelopoiesis Protein Tyrosine Phosphatases Granulocytes Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences. 103:2776-2781 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Protein tyrosine phosphatase 1B (PTP-1B) is a ubiquitously expressed cytosolic phosphatase with the ability to dephosphorylate JAK2 and TYK2, and thereby down-regulate cytokine receptor signaling. Furthermore, PTP-1B levels are up-regulated in certain chronic myelogenous leukemia patients, which points to a potential role for PTP-1B in myeloid development. The results presented here show that the absence of PTP-1B affects murine myelopoiesis by modifying the ratio of monocytes to granulocytesin vivo. This bias toward monocytic development is at least in part due to a decreased threshold of response to CSF-1, because the PTP-1B −/− bone marrow presents no abnormalities at the granulocyte–monocyte 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 −/− cells display increased inflammatory activityin vitroandin vivothrough 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 activationin vivoand provide a demonstration of a physiological role for PTP-1B in immune regulation. |
| Databáze: | OpenAIRE |
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