HIV-1 Tat mediates degradation of RON receptor tyrosine kinase, a regulator of inflammation.
J Immunol
; 181(2): 1548-55, 2008 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-18606710
ABSTRACT
HIV encodes several proteins, including Tat, that have been demonstrated to modulate the expression of receptors critical for innate immunity, including MHC class I, mannose receptor, and beta(2)-microglobulin. We demonstrate that Tat targets the receptor tyrosine kinase recepteur d'origine nantais (RON), which negatively regulates inflammation and HIV transcription, for proteosome degradation. Tat decreases cell surface RON expression in HIV-infected monocytic cells, and Tat-mediated degradation of RON protein is blocked by inhibitors of proteosome activity. Tat specifically induced down-regulation of RON and not other cell surface receptors, such as the transferrin receptor, the receptor tyrosine kinase TrkA, or monocytic markers CD14 and ICAM-1. The Tat trans activation domain is required for RON degradation, and this down-regulation is dependent on the integrity of the kinase domain of RON receptor. We propose that Tat mediates degradation of RON through a ubiquitin-proteosome pathway, and suggest that by targeting signals that modulate inflammation, Tat creates a microenvironment that is optimal for HIV replication and progression of AIDS-associated diseases.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
HIV-1
/
Receptores Proteína Tirosina Quinases
/
Produtos do Gene tat do Vírus da Imunodeficiência Humana
/
Macrófagos
Limite:
Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos