ABSTRACT
K+ channels are essential for a variety of cellular functions in both excitable and nonexcitable cells, and K+ channel gene alteration has been recently described in cardiac and neurological disorders. To explore further the relations between hereditary human diseases and K+ channels, we isolated from a human cosmid library the gene encoding the inwardly rectifying K+ channel alpha-subunit Kir 2.2 (KCNJ12). PCR analysis performed on this clone indicates that the entire open reading frame is contained in one unique exon. A polymorphic (CA)16 sequence was localized 2.2 kb upstream of the ATG start codon. Fluorescence in situ hybridization on human metaphases assigns the gene to band 17p11.1. The implication of a deletion of the Kir 2.2 gene in the Smith-Magenis syndrome, which is also localized at 17p11, is unlikely since a Kir 2.2-linked microsatellite sequence could be amplified from the DNA of a Smith-Magenis syndrome affected patient bearing a 17p interstitial deletion.
Subject(s)
Chromosome Mapping , Chromosomes, Human, Pair 17 , Dinucleotide Repeats , Polymorphism, Genetic , Potassium Channels, Inwardly Rectifying , Potassium Channels/genetics , Abnormalities, Multiple/genetics , Animals , Cell Line , Cloning, Molecular , Cricetinae , Exons , Female , Gene Deletion , Humans , In Situ Hybridization, Fluorescence , Introns , Male , Mice , Molecular Sequence Data , SyndromeABSTRACT
Considering the eventuality of an interaction between the two post-translational modifications, phosphorylation and ADP-ribosylation, we investigated the possibility of phosphorylation of the mRNP polyADPR polymerase by a protein kinase C associated to these particles. We demonstrated that cytoplasmic poly (ADP-ribose) polymerase associated with ribonucleoprotein particles containing silent mRNA is phosphorylated by a specifically activated endogenous protein kinase C which in turn induces an inhibition of the polymerase activity. In the absence of protein kinase C activators the mRNP polyADPR-P is also phosphorylated but without changes of its enzymatic activity.
