T cell receptor-dependent tyrosine phosphorylation of beta2-chimaerin modulates its Rac-GAP function in T cells.
J Biol Chem
; 284(17): 11354-63, 2009 Apr 24.
Article
em En
| MEDLINE
| ID: mdl-19201754
ABSTRACT
The actin cytoskeleton has an important role in the organization and function of the immune synapse during antigen recognition. Dynamic rearrangement of the actin cytoskeleton in response to T cell receptor (TCR) triggering requires the coordinated activation of Rho family GTPases that cycle between active and inactive conformations. This is controlled by GTPase-activating proteins (GAP), which regulate inactivation of Rho GTPases, and guanine exchange factors, which mediate their activation. Whereas much attention has centered on guanine exchange factors for Rho GTPases in T cell activation, the identity and functional roles of the GAP in this process are largely unknown. We previously reported beta2-chimaerin as a diacylglycerol-regulated Rac-GAP that is expressed in T cells. We now demonstrate Lck-dependent phosphorylation of beta2-chimaerin in response to TCR triggering. We identify Tyr-153 as the Lck-dependent phosphorylation residue and show that its phosphorylation negatively regulates membrane stabilization of beta2-chimaerin, decreasing its GAP activity to Rac. This study establishes the existence of TCR-dependent regulation of beta2-chimaerin and identifies a novel mechanism for its inactivation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tirosina
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Receptores de Antígenos de Linfócitos T
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Linfócitos T
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Proteínas rac de Ligação ao GTP
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Proteínas de Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article