Tumor necrosis factor induces phosphorylation of a 28-kDa mRNA cap-binding protein in human cervical carcinoma cells.
Tumor necrosis factor alpha (TNF-alpha) stimulated the phosphorylation of a 28-kDa protein (p28) in the ME-180 line of human cervical carcinoma cells. The effect of TNF-alpha on the phosphorylation state of p28 was rapid (4-fold increase within 15 min) and persistent, remaining above the basal level for at least 2 hr. The specific binding of 125I-labeled TNF-alpha to cell-surface binding sites, the stimulation of p28 phosphorylation by TNF-alpha, and the inhibition of cell proliferation by TNF-alpha occurred with nearly identical dose-response relationships. Two-dimensional SDS/PAGE resolved p28 into two isoforms having pI values of 6.2 and 6.1. A phosphorylated cap-binding protein was substantially enriched from lysates of control or TNF-alpha-treated ME-180 cells by affinity chromatography with 7-methylguanosine 5'-triphosphate-Sepharose. The phosphoprotein recovered from this procedure was the substrate for TNF-alpha-promoted phosphorylation, p28. Thus, TNF-alpha stimulates the phosphorylation of this mRNA cap-binding protein, which may be involved in the transduction of TNF-alpha-receptor binding into cellular responses.
Marino
M W
MW
Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Pfeffer
L M
LM
Guidon
P T
PT
Donner
D B
DB
D002352:Carrier Proteins / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D007700:Kinetics; D008970:Molecular Weight; D010750:Phosphoproteins / Q000096:biosynthesis / Q000302:isolation & purification; D010766:Phosphorylation; D039381:RNA Cap-Binding Proteins; D012315:RNA Caps / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms
D002352:Carrier Proteins; D010750:Phosphoproteins; D039381:RNA Cap-Binding Proteins; D012315:RNA Caps; D014409:Tumor Necrosis Factor-alpha