Activation of p21-activated kinase 2 by human immunodeficiency virus type 1 Nef induces merlin phosphorylation.
The accessory human immunodeficiency virus type 1 (HIV-1) protein Nef activates the autophosphorylation activity of p21-activated kinase 2 (PAK2). Merlin, a cellular substrate of PAK2, is homologous to the ezrin-radixin-moesin family and plays a critical role in Rac signaling. To assess the possible impact on host cell metabolism of Nef-induced PAK2 activation, we investigated the phosphorylation of merlin in Nef expressing cells. Here we report that Nef induces merlin phosphorylation in multiple cell lines independently of protein kinase A. This intracellular phosphorylation of merlin directly correlates with in vitro assay of the autophosphorylation activity of Nef-activated PAK2. Importantly, merlin phosphorylation induced by Nef was also observed in human primary T cells. The finding that Nef induces phosphorylation of the key signaling molecule merlin suggests several possible roles for PAK2 activation in HIV pathogenesis.
Wei
Bangdong L
BL
Department of Internal Medicine, Division of Infectious Diseases, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.
Arora
Vivek K
VK
Raney
Alexa
A
Kuo
Lillian S
LS
Xiao
Guang-Hui
GH
O'Neill
Eduardo
E
Testa
Joseph R
JR
Foster
John L
JL
Garcia
J Victor
JV
D002460:Cell Line; D004789:Enzyme Activation; D015693:Gene Products, nef / Q000235:genetics / Q000502:physiology*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D025581:Neurofibromin 2 / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D054311:nef Gene Products, Human Immunodeficiency Virus; D054462:p21-Activated Kinases
D015693:Gene Products, nef; D025581:Neurofibromin 2; D054311:nef Gene Products, Human Immunodeficiency Virus; C515907:PAK2 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases