Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Relative to resting liver, Morris hepatomas with different growth rates (3924A, 5123D, 7800, and 7777) all had higher (two to eightfold) levels (activity/gm tissue) of RNA polymerase I. Only the most rapidly growing tumor (hepatoma 3924A) showed a substantial increase (fivefold) in RNA polymerase III activity. RNA polymerase II activity/gm tissue in the hepatomas was similar to that in resting liver. The elevation in the hepatoma RNA polymerase I activity resulted from both an increase in the number of transcriptionally active enzyme molecules and an increase in the specific activity of the enzyme as a result of phosphorylation. Phosphorylation of RNA polymerase I from Morris hepatoma 3924A could be catalyzed either by an endogenous protein kinase or by a highly purified preparation of NII protein kinase from the same tumor. Three out of eight polypeptides (Mr 120,000, 65,000, and 25,000) or RNA polymerase I were phosphorylated. Phosphorylation resulted in enhanced RNA synthesis at the level of chain elongation. Another nuclear protein kinase, NI, had no significant effect on RNA polymerase I. The activity and/or amount of the NII protein kinase was significantly reduced in resting liver, which correlated with decreased specific activity of the liver RNA polymerase I. Anti-RNA polymerase I antibodies were found in the sera of patients with rheumatic autoimmune diseases such as systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), and rheumatoid arthritis (RA). Sera from these patients were capable of specifically inhibiting RNA polymerase I activity in vitro. Antibodies were produced predominantly against three of the polypeptides--S3 (Mr 65,000), S4 (Mr 42,000), and S5 (Mr 25,000) of RNA polymerase I. The spectrum and proportion of the antibodies against these three subunits differ with each patient and with the type of the autoimmune disease. These observations indicate that (1) the NII kinase can regulate RNA polymerase I activity, (2) protein kinase NII is associated with the polymerase I enzyme complex, and (3) certain polypeptides of this enzyme complex may be the target antigens in rheumatic autoimmune disease.
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PMID:Regulation of RNA polymerase I by phosphorylation and production of anti-RNA polymerase I antibodies in rheumatic autoimmune diseases. 660 44

Antibodies against nuclear protein kinase NII were detected by radioimmunoassay in the sera of patients with systemic lupus erythematosus and mixed connective tissue disease but not in sera from normal individuals or from patients with rheumatoid arthritis. Immunoglobulins derived from sera containing the anti-kinase antibodies inhibited the activity of protein kinase NII in vitro but had no effect on the activity of cytoplasmic cyclic AMP-dependent protein kinase.
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PMID:Anti-protein kinase NII antibodies in rheumatic autoimmune diseases. 669 57

In this study we determined the prevalence of autoantibodies against casein kinase II (CKII) in patients positive for anti-70K marker antibodies, which is indicative of mixed connective tissue disease. An anti-CKII ELISA was established with the use of bacterially expressed recombinant CKII proteins. Eight out of 52 anti-70K-positive sera (15%) were positive for anti-CKII antibodies, which recognized preferentially the CKII alpha subunit. All control sera (n = 52) were anti-CKII negative. Thus, the occurrence of anti-CKII antibodies may be of value for differential diagnosis.
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PMID:Antibodies to casein kinase II in sera of patients with mixed connective tissue disease: evaluation with recombinant proteins. 825 20

Sera from patients with systemic lupus erythematosus, polymyositis, scleroderma, and mixed connective tissue disease are frequently characterized by the presence of high levels of autoantibodies directed against linked sets of nuclear proteins. One of these autoantigen systems is made up of Ku and the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), proteins that are essential for double-strand DNA break repair and for the related process of V(D)J recombination. Ku and DNA-PKcs bind avidly to DNA ends in vivo and in vitro and form an active protein kinase complex. One hypothesis is that this assembled nucleoprotein particle, rather than its component proteins, is a primary trigger for the autoimmune response and thus a major target for the resulting autoantibodies. To screen for particle-specific antibodies, we developed an assay in which the fully native nucleoprotein particle is reconstituted in vitro and is tethered to the surface of an ELISA plate via a streptavidin-biotin linkage. These particles are recognized efficiently by monoclonal antibodies and by autoantibodies present in patient sera. The assay may detect a broader spectrum of epitopes than a conventional ELISA in which Ku and DNA-PKcs are adsorbed directly to a plastic surface. The method will be advantageous for high-throughput screening for antibodies and other ligands that bind the assembled DNA-dependent protein kinase complex.
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PMID:A method to detect particle-specific antibodies against Ku and the DNA-dependent protein kinase catalytic subunit in autoimmune sera. 1129 81