HIV Nef, paxillin, and Pak1/2 regulate activation and secretion of TACE/ADAM10 proteases

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autorinnen und Autoren: Lee JH, Wittki S, Braeu T, Dreyer F, Kraetzel K, Dindorf J, Johnston ICD, Gross S, Kremmer E, Zeidler R, Schlötzer-Schrehardt U, Lichtenheld M, Saksela K, Harrer T, Schuler G, Federico M, Baur A
Zeitschrift: Molecular Cell
Jahr der Veröffentlichung: 2013
Band: 49
Heftnummer: 4
Seitenbereich: 668-79
ISSN: 1097-2765


Abstract


The HIV Nef protein recruits the polycomb protein Eed and mimics an integrin receptor signal for reasons that are not entirely clear. Here we demonstrate that Nef and Eed complex with the integrin effector paxillin to recruit and activate TNF? converting enzyme (TACE alias ADAM 17) and its close relative ADAM10. The activated proteases cleaved proTNF? and were shuttled into extracellular vesicles (EVs). Peripheral blood mononuclear cells that ingested these EVs released TNF?. Analyzing the mechanism, we found that Pak2, an established host cell effector of Nef, phosphorylated paxillin on Ser272/274 to induce TACE-paxillin association and shuttling into EVs via lipid rafts. Conversely, Pak1 phosphorylated paxillin on Ser258, which inhibited TACE association and lipid raft transfer. Interestingly, melanoma cells used an identical mechanism to shuttle predominantly ADAM10 into EVs. We conclude that HIV-1 and cancer cells exploit a paxillin/integrin-controlled mechanism to release TACE/ADAM10-containing vesicles, ensuring better proliferation/growth conditions in their microenvironment.



FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Dreyer, Florian Dr. rer. nat.
Hautklinik
Harrer, Thomas Prof. Dr.
Professur für Innere Medizin mit dem Schwerpunkt Immundefizienz
Schlötzer-Schrehardt, Ursula apl. Prof. Dr.
Medizinische Fakultät
Schuler, Gerold Prof. Dr.
Lehrstuhl für Haut- und Geschlechtskrankheiten


Zusätzliche Organisationseinheit(en)
Augenklinik


Einrichtungen weiterer Autorinnen und Autoren

Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU)
Helsingin yliopisto / University of Helsinki
Istituto Superiore di Sanità (ISS)
Ludwig-Maximilians-Universität (LMU)
Miltenyi Biotec GmbH
University of Miami


Zitierweisen

APA:
Lee, J.-H., Wittki, S., Braeu, T., Dreyer, F., Kraetzel, K., Dindorf, J.,... Baur, A. (2013). HIV Nef, paxillin, and Pak1/2 regulate activation and secretion of TACE/ADAM10 proteases. Molecular Cell, 49(4), 668-79. https://dx.doi.org/10.1016/j.molcel.2012.12.004

MLA:
Lee, Jung-Hyun, et al. "HIV Nef, paxillin, and Pak1/2 regulate activation and secretion of TACE/ADAM10 proteases." Molecular Cell 49.4 (2013): 668-79.

BibTeX: 

Zuletzt aktualisiert 2019-22-07 um 07:31