Tyrosine phosphorylation of phospholipase C-gamma 1 by vaccinia virus growth factor.
Vaccinia virus growth factor (VGF), a highly glycosylated polypeptide encoded in the genome of vaccinia virus, shares amino acid sequence homology and functional properties with cellular growth factors, EGF and TGF-alpha. Although the mitogenic activity of the purified or synthetic VGF suggested that the factor may be beneficial for viral replication by stimulation of host cell growth, neither the role in virus life cycle nor the step next to the EGF receptor activation had been firmly established. We found tyrosine-phosphorylations of PLC-gamma 1 and concomitant increase of the phosphoinositides level in the human epidermoidal A431 cells either treated with purified VGF or infected with vaccinia virus. In contrast to the wild-type virus, a VGF- mutant virus did not induce tyrosine phosphorylation of PLC-gamma 1. Phosphopeptide analysis indicated that the phosphorylation of the PLC-gamma 1 by VGF includes tyrosine residues identical to those phosphorylated by EGF. These results suggest that tyrosine phosphorylation of PLC-gamma 1, mediated by VGF, leads to activation of PLC-gamma 1 and a concomitant increase in phosphatidylinositol turnover.
Department of Life Science, Pohang University of Science and Technology, Korea.
H S
HS
Kim
Y H
YH
Lee
D S
DS
Min
J S
JS
Chang
S H
SH
Ryu
B Y
BY
Ahn
P G
PG
Suh
D016475:3T3 Cells; D000818:Animals; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000378:metabolism; D006133:Growth Substances / Q000302:isolation & purification / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D010455:Peptides / Q000302:isolation & purification / Q000378:metabolism*; D051966:Phospholipase C gamma; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*; D014616:Vaccinia virus / Q000378:metabolism*; D014764:Viral Proteins / Q000302:isolation & purification / Q000378:metabolism*
D006133:Growth Substances; D007295:Inositol Phosphates; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D014764:Viral Proteins; C051087:vaccinia growth factor; D014443:Tyrosine; D004815:Epidermal Growth Factor; D010738:Type C Phospholipases; D051966:Phospholipase C gamma