Molecular cloning and characterization of the human double-stranded RNA-activated protein kinase induced by interferon.
The double-stranded (ds) RNA-activated protein kinase from human cells is a 68 kd protein (p68 kinase) induced by interferon. On activation by dsRNA in the presence of ATP, the kinase becomes autophosphorylated and can catalyze the phosphorylation of the alpha subunit of eIF2, which leads to an inhibition of the initiation of protein synthesis. Here we report the molecular cloning and characterization of several related cDNAs from which can be deduced the full-length p68 kinase sequence. All of the cDNAs identify a 2.5 kb RNA that is strongly induced by interferon. The deduced amino acid sequence of the p68 kinase predicts a protein of 550 amino acids containing all of the conserved domains specific for members of the protein kinase family, including the catalytic domain characteristic of serine/threonine kinases. In vitro translation of a reconstructed full-length p68 kinase cDNA yields a protein of 68 kd that binds dsRNA, is recognized by a monoclonal antibody raised against the native p68 kinase, and is autophosphorylated.
Meurs
E
E
Institut Pasteur Unité d'Oncologie Virale-URA CNRS 1157, Paris, France.
Chong
K
K
Galabru
J
J
Thomas
N S
NS
Kerr
I M
IM
Williams
B R
BR
Hovanessian
A G
AG
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D015152:Blotting, Northern; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004790:Enzyme Induction; D006801:Humans; D007372:Interferons; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D012330:RNA, Double-Stranded; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D019892:eIF-2 Kinase
D010750:Phosphoproteins; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D004247:DNA; D007372:Interferons; D011494:Protein Kinases; D019892:eIF-2 Kinase