Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The proteins which have been left tightly bound to the tissue culture substrate after ethylenebis (oxyethyl-enenitrilo) tetraacetic acid (EGTA)-mediated removal of normal, virus-transformed, and revertant mouse cells and which have been implicated in the substrate adhesion process have been analyzed by slab sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Three size classes of hyaluronate proteoglycans were resolved in the 5% well gel; approximately half of the protein in the substrate-attached material coelectrophoresed with these polysaccharides-so-called glycosaminoglycan-associated protein(GAP). A portion of the GAP was shown to be highly heterogeneous and displaced from the polysaccharide by preincubation with calf histone before electrophoresis. The relative proportions of the proteoglycans varied in material deposited during a variety of cellular attachment and growth conditions. The remainder of the cellular protein in substrate-attached material was resolved as several major and distinct protein bands in 8 or 20% separating gels (a limited number of distinct serum proteins have also been identified as substrate bound). Protein C0 (molecular weight 220 000) was a prominent component in the material from a variety of normal and virus-transformed cells and resembled the so-called LETS or CSP glycoprotein in several respects; protein Ca was myosin-like in several respects; protein C2 was shown to be actin; and protein C1 (molecular weight 56 000) does not appear to be tubulin. Histones were also present in most preparations of substrate-attached material, particularly at high levels in transformed cell meterial, and may result from EGTA-mediated leakiness of the cell and subsequent binding to the negatively charged polysaccharide. These substrate-attached proteins were (a) prominent in substrate-attached material from many cell types in characteristic relative proportions, (b) deposited by EGTA-subcultured cells during the first hour of attachment to fresh substrate, (c) deposited by cells growing on plastic or glass substrates (three additional) components were also prominent in glass-attached material), and (d) deposited during long-term growth on or initial attachment to substrates coated wit 3T3 substrate-attached material. Pulse-chase analyses with radioactive leucine indicated that these proteins exhibit different turn-over behaviors. These results are discussed with regard to the possible involvement of these substrate-attached proteins in the substrate adhesion process, with particular interest in the interaction of cytoskeletal microfilaments with other surface membrane components and with regard to alteration of substrate adhesion by virus transformation.
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PMID:Electrophoretic analysis of substrate-attached proteins from normal and virus-transformed cells. 18 10

The rat perineal levator ani (LA) and bulbocavernosus (BC) muscles are homogeneously type 2B fibers as determined by Ca, Mg-ATPase activity. The LA and extensor digitorum longus (EDL) muscles contain similar quantities of creatine kinase and several glycolytic enzymes despite significant differences in fiber composition. The LA muscles synthesizes and accumulates only the fast isoforms of protein C, myosin heavy chain and myosin light chains.
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PMID:Protein phenotype and gene expression in the rat perineal levator ani muscle. 397 33

The effect of chronic dexamethasone treatment was investigated on the myofibriller proteins of slow (soleus) and fast (semimembranous) muscles. The relative quantities of actin, protein C and protein M increased, while the myosin, troponin inhibitor and calcium binding components showed a relative decrease in both muscle types. The amount of troponin regulatory component and alpha-actinin decreased only in the fast muscle, while tropomyosin decreased significantly in the slow muscle. The isoenzyme pattern of fast muscle myosin was altered as a consequence of decreased myosin (LC-3 subunit.
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PMID:Changes in the contractile proteins of skeletal muscles induced by steroid myopathy. 699 31

Myosin-binding-protein C (MyBP-C) is a myosin-associated protein of unknown function found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. Using a cDNA clone encoding the fast-type isoform of chicken MyBP-C, we screened a human fetal muscle cDNA library and isolated clones encoding the full-length human fast-type isoform of MyBP-C. cDNA clones encoding the slow-type isoform of human MyBP-C, were also isolated and fully sequenced. Northern-blot analysis demonstrated skeletal muscle-specific expression of these gene products. Using human/hamster somatic-cell hybrids, we were able to map the slow-type MyBP-C to human chromosome 12, and the fast-type MyBP-C to chromosome 19. The cDNA for human fast-type MyBP-C encodes a polypeptide of 1142 amino acids with an expected molecular mass of 128.1 kDa. Comparison of this cDNA with other members of the MyBP family reveals extensive primary-sequence conservation. Each MyBP-C contains seven immunoglobulin C2 motifs and three fibronectin type-III repeats in the arrangement C2-C2-C2-C2-C2-III-III-C2-III-C2. Regions of high identity shared by the chicken and the two human proteins are not restricted to the immunoglobulin and fibronectin motifs. Sequence comparison of all three proteins has allowed us to map a highly conserved region between the first and second C2 motifs, the only large spacer sequence present between motifs in these proteins.
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PMID:Complete sequence of human fast-type and slow-type muscle myosin-binding-protein C (MyBP-C). Differential expression, conserved domain structure and chromosome assignment. 837

The thick filaments of vertebrate striated muscles contain with myosin a number of accessory proteins of the intracellular immunoglobulin superfamily, which are localized in a distinct pattern of stripes 43 nm apart. The specific localization of these proteins is believed to be due partly to their interaction with the giant muscle protein titin (also called connectin), which spans the entire sarcomere and may act as a molecular ruler. We have used recombinant fragments of titin covering the thick filament region to investigate their interaction with myosin-binding protein C (MyBP-C) from skeletal and cardiac muscle. The interaction of titin and MYBP-C is directed by a subset of titin immunoglobulin domains that are specific for the C-region of the thick filament, supporting the ruler hypothesis for the myosin-binding proteins. The interaction of recombinant titin with overlapping fragments of human cardiac MyBP-C maps the titin-binding site within the C-terminal region, which is deleted in patients suffering from the chromosome-11-associated form of familial hypertrophic cardiomyopathy. This disorder is therefore likely to be the result of thick-filament misassembly by abolishing the ternary interaction of titin, myosin and MyBP-C.
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PMID:A molecular map of the interactions between titin and myosin-binding protein C. Implications for sarcomeric assembly in familial hypertrophic cardiomyopathy. 863 48

Mutations in several muscle structural proteins (the myosin heavy chain, alpha tropomyosin, cardiac troponin T and myosin binding protein C) result in a genetically dominant heart disease, hypertrophic cardiomyopathy. Biochemical data from studies of mutant myosin suggest a dominant-negative mechanism for inheritance of this disease. The most likely primary defect is sarcomere dysfunction, which is followed by the major clinical symptoms.
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PMID:Contractile protein mutations and heart disease. 879 11

In addition to the contractile proteins actin and myosin, contractile filaments of striated muscle contain other proteins that are important for regulating the structure and the interaction of the two force-generating proteins. In the thin filaments, troponin and tropomyosin form a Ca-sensitive trigger that activates normal contraction when intracellular Ca is elevated. In the thick filament, there are several myosin-binding proteins whose functions are unclear. Among these is the myosin-binding protein C (MBP-C). The cardiac isoform contains four phosphorylation sites under the control of cAMP and calmodulin-regulated kinases, whereas the skeletal isoform contains only one such site, suggesting that phosphorylation in cardiac muscle has a specific regulatory function. We isolated natural thick filaments from cardiac muscle and, using electron microscopy and optical diffraction, determined the effect of phosphorylation of MBP-C on cross bridges. The thickness of the filaments that had been treated with protein kinase A was increased where cross bridges were present. No change occurred in the central bare zone that is devoid of cross bridges. The intensity of the reflections along the 43-nm layer line, which is primarily due to the helical array of cross bridges, was increased, and the distance of the first peak reflection from the meridian along the 43-nm layer line was decreased. The results indicate that phosphorylation of MBP-C (i) extends the cross bridges from the backbone of the filament and (ii) increases their degree of order and/or alters their orientation. These changes could alter rate constants for attachment to and detachment from the thin filament and thereby modify force production in activated cardiac muscle.
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PMID:Alteration of myosin cross bridges by phosphorylation of myosin-binding protein C in cardiac muscle. 879 43

In recent years, the striking development of molecular biology and molecular genetic has brought completely new insights into the understanding of heart failure. Two aspects for which significant progress has been made in 1995 are discussed in this review: the genetic mechanisms of inherited cardiomyopathies and the molecular basis of heart failure due to chronic hemodynamic overload. In familial hypertrophic cardiomyopathy, a novel disease gene was found. It encodes myosin binding protein C, whose structure and function are poorly understood. Contractile deficits associated with the myosin mutations were demonstrated, and all this strengthened the hypothesis that hypertrophy is a compensatory mechanism that occurs in presence of a sarcomeric defect. These studies have important prognostic and clinical implications, but new and unexpected concerns have arisen, because a widespread difference in phenotype can be seen in patients harboring similar genotypes. In familial dilated cardiomyopathy, the main findings were the identification of four disease loci, but the genes are still unknown. With respect to the consequences of chronic hemodynamic overload on myocyte function and phenotype, recent data gave rise to lively discussions in the fields of reexpression of fetal troponin T isoforms and of decreased function and expression of the sarco(endo)plasmic reticulum Ca2+ ATPase in the failing human heart; at the moment it is difficult to draw definitive conclusions. Interestingly, three new concepts emerged in the understanding of the pathogenesis of heart failure: the increased contribution of the Na(+)-Ca2+ exchange, the possible recruitment of an inositol phosphate-sensitive calcium pool for myofibrillar activation, and the involvement of apoptotic myocyte and nonmyocyte cell death in myocardial remodeling.
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PMID:Molecular and cellular biology of heart failure. 883 64

Mutations in the gene for the cardiac isoform of myosin binding protein C (MyBP-C) have been identified as the cause of chromosome 11-associated autosomal-dominant familial hypertrophic cardiomyopathy (FHC). Most mutations produce a truncated polypeptide that lacks the sarcomeric binding region. We have now investigated the expression pattern of the cardiac and skeletal isoforms of cMyBP-C in mice and humans by in situ hybridization and immunofluorescence microscopy using specific antibodies and probes. We demonstrate that the cardiac isoform is expressed only in cardiac muscle throughout development. The slow and fast isoforms of MyBP-C remain specific for skeletal muscle, where they can be coexpressed. Immunological evidence also suggests that an embryonic isoform of MyBP-C precedes the expression of slow MyBP-C in developing skeletal muscle. This suggests that transcomplementation of MyBP-C isoforms is possible in skeletal but not cardiac muscle.
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PMID:Isoform transitions of the myosin binding protein C family in developing human and mouse muscles: lack of isoform transcomplementation in cardiac muscle. 944 Jul 11

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease caused by mutations in sarcomeric proteins. The disease is characterized by left ventricular hypertrophy in the absence of an increased external load, and myofibrillar disarray. A large number of mutations in genes coding for the beta-myosin heavy chain (beta-MyHC), cardiac troponin T (cTnT), cardiac troponin I, alpha-tropomyosin, myosin binding protein C (MyBP-C), and myosin light chain 1 and 2 in patients with HCM have been identified. Genotype-phenotype correlation studies have shown that mutations carry prognostic significance. The Gly256Glu, Val606Met, and Leu908Val mutations in the beta-MyHC are associated with a benign prognosis. In contrast, Arg403Gln, Arg719Trp, and Arg453Cys mutations are associated with a high incidence of sudden cardiac death (SCD). Mutations in cTnT are associated with a mild degree of hypertrophy, but a high incidence of SCD. Mutations in MyBP-C are associated with mild hypertrophy and a benign prognosis. However, it has become evident that factors other than the underlying mutations, such as genetic background and possibly environmental factors, also modulate phenotypic expression of HCM.
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PMID:Molecular genetic basis of hypertrophic cardiomyopathy: genetic markers for sudden cardiac death. 947 82


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