Essential roles for the Tec family kinases Tec and Btk in M-CSF receptor signaling pathways that regulate macrophage survival

Autor: Bernd Unger, Wilfried Ellmeier, Kari Alitalo, Uwe Schmidt, Martin Melcher, Iiro Rajantie
Rok vydání: 2008
Předmět:
Macrophage colony-stimulating factor
Cell Survival
TEC
Cellular differentiation
Immunology
education
Bone Marrow Cells
Receptor
Macrophage Colony-Stimulating Factor
Article
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Agammaglobulinaemia Tyrosine Kinase
Immunology and Allergy
Bruton's tyrosine kinase
Animals
Myeloid Cells
Cells
Cultured
030304 developmental biology
Mice
Knockout
0303 health sciences
biology
Kinase
Macrophage Colony-Stimulating Factor
Tyrosine phosphorylation
hemic and immune systems
Cell Differentiation
Protein-Tyrosine Kinases
Caspases
Initiator
Cell biology
Mice
Inbred C57BL
Protein Subunits
chemistry
Caspases
Multigene Family
biology.protein
Cancer research
Macrophages
Peritoneal
Phosphorylation
Signal transduction
tissues
030215 immunology
Signal Transduction
Zdroj: ResearcherID
ISSN: 0022-1767
Popis: Tec family kinases have important roles in lymphocytes; however, little is known about their function in monocytes/macrophages. In this study we report that Tec family kinases are essential for M-CSF (M-CSF)-induced signaling pathways that regulate macrophage survival. Compared with wild-type bone marrow-derived macrophage (BMM) cultures, Tec−/−Btk−/− BMM cultures displayed increased cell death that correlated with a severe drop in macrophage numbers. In addition, macrophages deficient in either Tec or Btk showed expression and activation of caspase-11. Elucidation of M-CSF receptor (M-CSFR) signaling pathways revealed that the total tyrosine phosphorylation pattern upon M-CSF stimulation was altered in Tec−/−Btk−/− macrophages despite normal expression and phosphorylation of the M-CSFR. Further, Tec and Btk are required for proper expression of the GM-CSF receptor α (GM-CSFRα) chain in macrophages but not dendritic cells, implicating Tec family kinases in the lineage-specific regulation of GM-CSFRα expression. Taken together, our study shows that Tec and Btk regulate M-CSFR signaling-induced macrophage survival and provides a novel link between Tec family kinases and the regulation of caspase-11 and GM-CSFRα expression.
Databáze: OpenAIRE
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