HIV-1 Nef Mediates Pak Phosphorylation of Mek1 Serine298 and Elicits an Active Phospho-state of Pak2

Title:HIV-1 Nef Mediates Pak Phosphorylation of Mek1 Serine298 and Elicits an Active Phospho-state of Pak2

Volume: 11 Issue: 3

Author(s): Arlette Kouwenhoven, Violette Der Minassian and Jon W. Marsh

Affiliation:

Keywords: Nef, Pak, Mek, kinase, T cell, phosphorylation.

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.

Cite this article as:

Kouwenhoven Arlette, Minassian Der Violette and Marsh W. Jon, HIV-1 Nef Mediates Pak Phosphorylation of Mek1 Serine298 and Elicits an Active Phospho-state of Pak2, Current HIV Research 2013; 11 (3) . https://dx.doi.org/10.2174/1570162X113119990039