Integrin and CD3/TCR activation are regulated by the scaffold protein AKAP450
During antigen recognition by T cells, membrane receptors and cytoskeletal molecules form a specialized structure at the T cell–antigen-presenting cell junction called the immune synapse (IS). We report a role for the scaffolding protein A-kinase anchoring protein-450 (AKAP450), a member of the A-ki...
| Autores: | , , , , , |
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| Formato: | artículo |
| Fecha de publicación: | 2010 |
| País: | España |
| Recursos: | Universidad Complutense de Madrid (UCM) |
| Repositorio: | Docta Complutense |
| Idioma: | inglés |
| OAI Identifier: | oai:docta.ucm.es:20.500.14352/94342 |
| Acesso em linha: | https://hdl.handle.net/20.500.14352/94342 |
| Access Level: | acceso abierto |
| Palavra-chave: | 576.3 577.112 577.27 Integrin CD3/TCRactivation Protein AKAP450 Biología celular (Biología) Bioquímica (Biología) Inmunología 2407 Biología Celular 2403 Bioquímica 2412 Inmunología |
| Resumo: | During antigen recognition by T cells, membrane receptors and cytoskeletal molecules form a specialized structure at the T cell–antigen-presenting cell junction called the immune synapse (IS). We report a role for the scaffolding protein A-kinase anchoring protein-450 (AKAP450), a member of the A-kinase anchoring protein family, in IS formation and T-cell signaling in antigen- and superantigen-dependent T-cell activation. Suppression of AKAP450 by overexpression of a dominant-negative form or siRNA knockdown disrupted the positioning and conformational activation of lymphocyte function-associated antigen 1 at the IS and impaired associated signaling events, including phosphorylation of phospholipase C-γ1 and protein kinase C-θ. AKAP450 was also required for correct activation and phosphorylation of CD3, LAT, and Vav1, key T-cell receptor-activated intracellular signaling molecules. Consistently, antigen-triggered reorientation of the microtubule-organizing center at the IS and interleukin-2 secretion were diminished in AKAP450-disrupted T cells. These results indicate key roles for AKAP450 in the organization and activation of receptor molecules at the IS during T-cell signaling events. |
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