Pseudorabies virus tegument protein Us2 recruits the mitogen-activated protein kinase extracellular-regulated kinase (ERK) to membranes through interaction with the ERK common docking domain.
The pseudorabies virus (PRV) Us2 protein binds to the extracellular-regulated kinase (ERK) and inhibits the activation of ERK nuclear targets by sequestering cytoplasmic ERK on cellular membranes. Utilizing a series of Us2 truncations, we determined that the minimal portion of Us2 required for interaction with ERK is contained within its amino-terminal 214 amino acids. The loss of the ability of Us2 to bind to ERK in coimmunoprecipitation experiments was accompanied by a failure of Us2 to form oligomers, raising the possibility that higher-order Us2 structures are required for ERK interaction. To map the Us2 interaction site on ERK, we introduced mutations into the region of ERK that interacts with the ERK kinase, MEK, or into the common docking (CD) domain that mediates interactions with many ERK substrates. ERK carrying mutations within the MEK binding region maintained the ability to bind Us2, whereas ERK carrying mutations within the CD domain did not. Furthermore, the ERK CD domain was required for the Us2-mediated recruitment of ERK to membranes. Taken together, these findings suggest that Us2 regulates ERK activity by spatially restricting ERK localization and also by interfering with select ERK-substrate interactions.
Kang
Ming-Hsi
MH
Department of Microbiology and Immunology, Queen's University, Kingston, Canada.
Banfield
Bruce W
BW
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology* / Q000821:virology; D002522:Chlorocebus aethiops; D011558:Herpesvirus 1, Suid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011557:Pseudorabies / Q000201:enzymology* / Q000821:virology; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D014759:Viral Envelope Proteins; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1