The human p68 kinase is an interferon‐regulated enzyme that inhibits protein synthesis when activated by double‐stranded RNA. We show here that when expressed in Saccharomyces cerevisiae, the p68 kinase produced a growth suppressing phenotype resulting from an inhibition of polypeptide chain initiation consistent with functional protein kinase activity. This slow growth phenotype was reverted in yeast by two different mechanisms: expression of the p68 kinase N‐terminus, shown to bind double‐stranded RNA in vitro and expression of a mutant form of the alpha‐subunit of yeast initiation factor 2, altered at a single phosphorylatable site. These results provide the first direct in vivo evidence that the p68 kinase interacts with the alpha‐subunit of eukaryotic initiation factor 2. Sequence similarity with a yeast translational regulator, GCN2, further suggests that this enzyme may be a functional homolog in higher eukaryotes, where its normal function is to regulate protein synthesis through initiation factor 2 phosphorylation.
The constitutive calcium/calmodulin-dependent nitric oxide (NO) syn~hasc cxprcsscd in vascular endothclium shams common biochcmjcal and pharmacologic properties with ncuronal NO synthasc. However. rcccnl cloning und molecular charaacrizalion of NO synthase from bovine endothclial cells indicated the existence of a family of constitutivo NO synlhascs. Accordingly, we undertook molecular cloning and scqucncc analysis of human cndothelial NO synthasc. Complemcruary DNA clones prcdicl a protein of 1,203 amino acids sharing 94% identity with the bovine cndothelial protein, but only 60% identity with the rut brain NO synlhasc isolbrm. Northern blot analysis with an endothclial-dcrivcdcDNA identitied a 4.6-4.8 kb mRNA transcript in IWVEC und in situ hybridization localized transcripts to vascular endothelium but not neuronal tissue.
Central core disease (CCD) is a morphologically distinct, autosomal dominant myopathy with variable clinical features. A close association with malignant hyperthermia (MH) has been identified. Since MH and CCD genes have been linked to the skeletal muscle ryanodine receptor (RYR1) gene, cDNA sequence analysis was used to search for a causal RYR1 mutation in a CCD individual. The only amino acid substitution found was an Arg2434His mutation, resulting from the substitution of A for G7301. This mutation was linked to CCD with a lod score of 4.8 at a recombinant fraction of 0.0 in 16 informative meioses in a 130 member family, suggesting a causal relationship to CCD.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.