HIV-1 Tat mediates degradation of RON receptor tyrosine kinase, a regulator of inflammation

Parisa Kalantari, Omid F. Harandi, Pamela A. Hankey, Andrew J. Henderson

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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 β2-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.

Original languageEnglish (US)
Pages (from-to)1548-1555
Number of pages8
JournalJournal of Immunology
Volume181
Issue number2
DOIs
StatePublished - Jul 15 2008

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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