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)

Myotrophin is a soluble-12 kilodalton protein isolated from hypertrophied spontaneously hypertensive rat and dilated cardiomyopathic human hearts. We have recently cloned the gene coding for myotrophin and expressed it in Escherichia coli. In the present study, the expression of myotrophin gene was analyzed, and at least seven transcripts have been detected in rat heart and in other tissues. We have further analyzed the primary structure of myotrophin protein and identified significant new structural and functional domains. Our analysis revealed that one of the ankyrin repeats of myotrophin is highly homologous specifically to those of myotrophin is highly homologous specifically to those of I kappa B alpha/rel ankyrin repeats. In addition, putative consensus phosphorylation sites for protein kinase C and casein kinase II, which were observed in I kappa B alpha proteins, were identified in myotrophin. To verify the significance of these homologies, kappa B gel shift assays were performed with Jurkat T cell nuclear extract proteins and the recombinant myotrophin. Results of these assays indicate that the recombinant myotrophin has the ability to interact with NF-kappa B/rel proteins as revealed by the formation of ternary protein-DNA complexes. While myotrophin-specific antibodies inhibited the formation of these complexes, rel-specific p50 and p65 antibodies supershifted these complexes. Thus, these results clearly indicate that the myotrophin protein to be a unique rel/NF-kappa B interacting protein.
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PMID:Cardiac myotrophin exhibits rel/NF-kappa B interacting activity in vitro. 857 59

To investigate how cardiac hypertrophy and heart failure develop, we isolated and characterized a candidate initiator, the soluble 12-kDa protein myotrophin, from rat and human hearts. Myotrophin stimulates protein synthesis and myocardial cell growth associated with increased levels of hypertrophy marker genes. Recombinant myotrophin from the cloned gene showed structural/functional motifs, including ankyrin repeats and putative phosphorylation sites for protein kinase C (PKC) and casein kinase II. One repeat, homologous with I kappaB, interacts with rel/NF-kappaB in vitro. We analyzed the interaction of recombinant myotrophin and nuclear extracts prepared from neonatal and adult cardiomyocytes; gel mobility shift assay showed that myotrophin bound to kappaB DNA. To define PKC's role in myotrophin-induced myocyte growth, we incubated neonatal rat myocytes (normal and stretch) with specific inhibitors and found that myotrophin inhibits [3H]leucine incorporation into myocytes and different hypertrophic gene expression in neonatal myocytes. Using confocal microscopy, we observed that a basal level of myotrophin was present in both cytoplasm and nucleus under normal conditions, but under cyclic stretch, myotrophin levels became elevated in the nucleus. Myotrophin gene levels were upregulated when myocytes underwent cyclic stretch or were treated with tumor necrosis factor-alpha (TNF-alpha) or interleukin-1beta and also when excised beating hearts were exposed to high pressure. Our data showed that the myotrophin-kappaB interaction was increased with age in spontaneously hypertensive rats (SHRs) only. Our data provide evidence that myotrophin-kappaB DNA interaction may be an important step in initiating cardiac hypertrophy.
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PMID:Myotrophin-kappaB DNA interaction in the initiation process of cardiac hypertrophy. 1203 92