Guanylate binding protein 1-mediated interaction of T cell antigen receptor signaling with the cytoskeleton.
J Immunol
; 192(2): 771-81, 2014 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-24337748
ABSTRACT
GTPases act as important switches in many signaling events in cells. Although small and heterotrimeric G proteins are subjects of intensive studies, little is known about the large IFN-inducible GTPases. In this article, we show that the IFN-γ-inducible guanylate binding protein 1 (GBP-1) is a regulator of T cell activation. Silencing of GBP-1 leads to enhanced activation of early T cell Ag receptor/CD3 signaling molecules, including Lck, that is translated to higher IL-2 production. Mass spectrometry analyses showed that regulatory cytoskeletal proteins, like plastin-2 that bundles actin fibers and spectrin ß-chain, brain 1 that links the plasma membrane to the actin cytoskeleton, are binding partners of GBP-1. The spectrin cytoskeleton influences cell spreading and surface expression of TCR/CD3 and the leukocyte phosphatase CD45. We found higher cell spreading and enhanced surface expression of TCR/CD3 and CD45 in GBP-1 silenced T cells that explain their enhanced TCR/CD3 signaling. We conclude that GBP-1 is a downstream processor of IFN-γ via which T cells regulate cytoskeleton-dependent cell functions.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Citoesqueleto
/
Receptores de Antígenos de Linfócitos T
/
Complexo Receptor-CD3 de Antígeno de Linfócitos T
/
Proteínas de Ligação ao GTP
Limite:
Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2014
Tipo de documento:
Article