The adenovirus E3-14.5K protein which is required for prevention of TNF cytolysis and for down-regulation of the EGF receptor contains phosphoserine.
The E3-14.5K and E3-10.4K proteins form a complex and function to down-regulate the epidermal growth factor receptor and to prevent tumor necrosis factor cytolysis in adenovirus-infected cells. Both 14.5K and 10.4K are cytoplasmic membrane proteins with a Ccyt orientation in the membrane. We show here that 14.5K is phosphorylated on serine residues in cells infected by adenoviruses that synthesize both 14.5K and 10.4K. 14.5K is phosphorylated on both serine and threonine in cells infected by a mutant that does not synthesize 10.4K; thus, the presence or absence of 10.4K affects the phosphorylation of 14.5K. Phosphotyrosine was not detected. 14.5K is also phosphorylated when translated in vitro in a rabbit reticulocyte extract. Both in vivo and in vitro, at least one of the phosphorylation sites is near the C-terminus, in the cytoplasmic domain of 14.5K. This C-terminal region of 14.5K is the most conserved among Ad5, Ad2, Ad3, and Ad7, and it is essential for 14.5K to prevent tumor necrosis factor cytolysis.
Krajcsi
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Institute for Molecular Virology, St. Louis University School of Medicine, Missouri 63110.
Wold
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WS
D017456:Adenovirus Early Proteins; D000260:Adenoviruses, Human / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D015536:Down-Regulation; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007624:KB Cells; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000737:chemistry* / Q000378:metabolism; D010449:Peptide Mapping; D010766:Phosphorylation; D010768:Phosphoserine / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017456:Adenovirus Early Proteins; D009856:Oncogene Proteins, Viral; D014409:Tumor Necrosis Factor-alpha; D010768:Phosphoserine; D066246:ErbB Receptors