A protein containing the cystic fibrosis antigen is an inhibitor of protein kinases.
To investigate myeloid cell maturation, we established a panel of monoclonal antibodies that recognize myeloid cell nuclear antigens. One of these monoclonal antibodies was used to purify a specific protein complex (PC) from a human spleen. This PC, which is present at high levels in peripheral blood monocytes and granulocytes, contains a protein that is the cystic fibrosis (CF) antigen. The purified PC was shown to inhibit the activity of casein kinase I and II but not cAMP-dependent protein kinase, protein kinase C, v-abl tyrosine kinase, or insulin receptor tyrosine kinase. The observed Ki values for casein kinases I and II purified from several sources were 1 microM or less. Furthermore, the addition of the purified PC to a nuclear extract from human cells was able to prevent protein kinase-mediated stimulation of RNA polymerase activity. The unique inhibitory character of the PC and its elevated levels in monocytes and granulocytes and of the CF antigen in CF patients implies that this complex may be associated with myeloid cell functions and perhaps with the cause or consequence of the clinical manifestations of CF.
Murao
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Division of Biological, Environmental and Medical Research, Argonne National Laboratory, Illinois 60439-4833.
Collart
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FR
Huberman
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D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000941:Antigens; D001483:Base Sequence; D001798:Blood Proteins / Q000032:analysis* / Q000235:genetics; D040501:Calgranulin A; D047388:Casein Kinases; D003550:Cystic Fibrosis; D004247:DNA / Q000235:genetics; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006098:Granulocytes / Q000032:analysis; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009000:Monocytes / Q000032:analysis; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D011506:Proteins / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D013154:Spleen / Q000032:analysis*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000941:Antigens; D001798:Blood Proteins; D040501:Calgranulin A; D047428:Protein Kinase Inhibitors; D011506:Proteins; C026422:cystic fibrosis serum factor; D004247:DNA; D011494:Protein Kinases; D047388:Casein Kinases; D012321:DNA-Directed RNA Polymerases