A protein containing the cystic fibrosis antigen is an inhibitor of protein kinases

• Published in: The Journal of biological chemistry Vol. 264; no. 14; pp. 8356 - 8360
• Main Authors: Murao, S, Collart, F R, Huberman, E
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 15.05.1989; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acid Sequence; Animals; Antibodies, Monoclonal; Antigens; Base Sequence; Biological and medical sciences; Blood Proteins - analysis; Blood Proteins - genetics; Calgranulin A; Casein Kinases; Cystic Fibrosis; DNA - genetics; DNA-Directed RNA Polymerases - metabolism; Female; Fluorescent Antibody Technique; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Granulocytes - analysis; Histocompatibility antigens (hla, h-2 and other systems); Humans; man; Mice; Mice, Inbred BALB C; Molecular immunology; Molecular Sequence Data; Monocytes - analysis; Protein Kinase Inhibitors; Protein Kinases - metabolism; Proteins - immunology; Proteins - isolation & purification; Proteins - pharmacology; spleen; Spleen - analysis; Tumor Cells, Cultured; Antigen; Ripening; Mucoviscidosis; Protein kinase C; Cystic fibrosis antigen; Purification; Gel electrophoresis; Protein kinase; Monoclonal antibody; Inhibition; Myeloid cell
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)83189-1

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 µM 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.