title: HIV-1 Nef mediates Pak phosphorylation of Mek1 serine298 and elicits an active phospho-state of Pak2.
abstract: The HIV-1 Nef protein brings about increased T cell activity and viral titers through mechanisms that are poorly understood. Nef activity has been described as an enhancer, but not an inducer, of certain signaling pathways that lead to T cell activation and viral production, particularly from resting T cells. The protein has also been found to associate with and promote autophosphorylation of a serine kinase, Pak2, but the Nef-associated kinase level is very low and difficult to study. Here we demonstrate that Nef expression mediates phosphorylation of Mek1 serine298 in T cell lines as well as primary human T cells, thus directly affecting the Erk cascade. This phosphorylation is through a Pak and Rac activity. We also find that Pak2 in Nef expressing cells is phosphorylated on serine192/197, the first biochemical description of the Nef-mediated activation state for this kinase.
authors.affiliation: Section on Directed Gene Transfer, Laboratory of Cellular and Molecular Regulation, NIMH, Bethesda, MD 20892-4483, USA.
authors.forename: Arlette
authors.initials: A
authors.lastname: Kouwenhoven
authors.forename: Violette Der
authors.initials: VD
authors.lastname: Minassian
authors.forename: Jon W
authors.initials: JW
authors.lastname: Marsh
mesh_terms: D002478:Cells, Cultured; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D013601:T-Lymphocytes / Q000201:enzymology / Q000821:virology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*; D054462:p21-Activated Kinases / Q000378:metabolism*
chemical_list: D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; C515907:PAK2 protein, human; D054462:p21-Activated Kinases; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human