HIV-1 Nef associated PAK and PI3-Kinases stimulate Akt-independent Bad-phosphorylation to induce ant
Author: ["Dietlinde Wolf","Vanessa Witte","Bernd Laffert","Katja Blume","Elisabeth Stromer","Susanna Trapp","Paola d'Aloja","Annette Schürmann","Andreas S. Baur"]
Publication: Nature Medicine
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Abstract
A highly conserved signaling property of Nef proteins encoded by human or simian immunodeficiency virus is the binding and activation of a PAK kinase whose function is unclear. Here we show that Nef-mediated p21-activated kinase (PAK) activation involves phosphatidylinositol 3-kinase, which acts upstream of PAK and is bound and activated by Nef similar to the manner of Polyoma virus middle T antigen. The Nef-associated phosphatidylinositol-3–PAK complex phosphorylated the pro-apoptotic Bad protein without involving the protein kinase B–Akt kinase, which is generally believed to inactivate Bad by serine phosphorylation. Consequently, Nef, but not a Nef mutant incapable of activating PAK, blocked apoptosis in T cells induced by serum starvation or HIV replication. Nef anti-apoptotic effects are likely a crucial mechanism for viral replication in the host and thus in AIDS pathogenesis.
Cite this article
Wolf, D., Witte, V., Laffert, B. et al. HIV-1 Nef associated PAK and PI3-Kinases stimulate Akt-independent Bad-phosphorylation to induce anti-apoptotic signals. Nat Med 7, 1217–1224 (2001). https://doi.org/10.1038/nm1101-1217
