Expression of the human MxA protein is associated with hyperphosphorylation of VSV P protein in human neural Cells.
Constitutive expression of the type I interferon-inducible human cytoplasmic MxA protein has been shown to interfere with primary transcription of vesicular stomatitis virus (VSV) in tissue culture cells. As phosphorylation of the VSV P protein has been linked to its ability to stimulate viral transcription, we analyzed the phosphorylation status of this protein in human brain cells (U-87) stably transfected with MxA. We observed a general increase in cellular kinase activity in the presence of MxA, affecting both cellular proteins and VSV P protein. Phosphorylation of the latter was up to threefold higher both in vivo and in vitro. In vitro phosphorylation of recombinant VSV P protein could be enhanced in MxA-negative cell extracts after exogenous addition of recombinant His-MxA. Biochemical evidence and phosphorylation of a mutant P protein lacking the recognized casein kinase II (CKII) sites suggested that hyperphosphorylation of VSV P protein was not due to a stimulation of CKII. We thus propose that expression of MxA in human brain cells is associated with the stimulation of a cellular kinase that is active in phosphorylating both cellular target proteins and VSV P protein.
Schuster
A
A
Institute for Virology, University of Würzburg, Germany.
Johnston
I C
IC
Das
T
T
Banerjee
A K
AK
Pavlovic
J
J
ter Meulen
V
V
Schneider-Schaulies
S
S
D047390:Casein Kinase II; D002460:Cell Line; D019204:GTP-Binding Proteins; D015870:Gene Expression; D006801:Humans; D064547:Myxovirus Resistance Proteins; D009474:Neurons / Q000378:metabolism / Q000821:virology*; D010750:Phosphoproteins; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000378:metabolism*; D015678:Viral Structural Proteins / Q000378:metabolism*
C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; C081250:P protein, Vesicular stomatitis virus; D010750:Phosphoproteins; D011506:Proteins; D015678:Viral Structural Proteins; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D019204:GTP-Binding Proteins