Abl Family Kinases Modulate T Cell–Mediated Inflammation and Chemokine-Induced Migration Through a HEF1-Rap1 Signaling Module
| Autor: | Erik J. Soderblom, Elena N. Pugacheva, Ann Marie Pendergast, M. Arthur Moseley, Catherine Lavau, Jing Jin Gu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
T-Lymphocytes
T cell Blotting Western Biology Time-Lapse Imaging Biochemistry Article Mice chemistry.chemical_compound Chemokine receptor Cell Movement hemic and lymphatic diseases Cell Adhesion medicine Animals Humans Phosphorylation Molecular Biology Adaptor Proteins Signal Transducing Inflammation ABL Kinase Tyrosine phosphorylation Cell Biology Protein-Tyrosine Kinases Phosphoproteins Cell biology medicine.anatomical_structure chemistry Cancer research Guanosine Triphosphate Chemokines Signal transduction Tyrosine kinase Signal Transduction |
| Popis: | Chemokine signaling is critical for T cell function during homeostasis and inflammation and directs T cell polarity and migration through the activation of specific intracellular pathways. Here, we uncovered a previously uncharacterized role for the Abl family tyrosine kinases Abl and Arg in the regulation of T cell-dependent inflammatory responses and showed that the Abl family kinases were required for chemokine-induced T cell polarization and migration. Our data demonstrated that Abl and Arg were activated downstream of chemokine receptors and mediated the chemokine-induced tyrosine phosphorylation of human enhancer of filamentation 1 (HEF1), an adaptor protein that is required for the activity of the guanosine triphosphatase Rap1, which mediates cell adhesion and migration. Phosphorylation of HEF1 by Abl family kinases and activation of Rap1 were required for chemokine-induced T cell migration. Mouse T cells that lacked Abl and Arg exhibited defective homing to lymph nodes and impaired migration to sites of inflammation. These findings suggest that Abl family kinases are potential therapeutic targets for the treatment of T cell-dependent immune disorders that are characterized by chemokine-mediated inflammation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|