Abstract
Background Nitric oxide signaling through the cGMP kinase (cGK1a) activates Myosin Phosphatase (MP) leading to calcium de-sensitization of force production. Leucine zipper (LZ) motifs present in the C-terminus of MYPT1 and N-terminus of cGK1a are thought to be essential for the hetero-dimerization of cGK1 and MYPT1 and cGK1 activation of MP [1]. An isoform of MYPT1 that lacks the C-terminal LZ motif is generated by the alternative splicing of a 31 nt 3’ exon (E23). We have shown that the expression of these MYPT1 isoforms is tissuespecific, developmentally regulated and modulates in disease [2]. MYPT1 E23-/LZ+ isoform is expressed in tonic smooth muscle of the large arteries and veins while MYPT1 E23+/LZisoform is expressed in the phasic smooth muscle of the intestines, portal vein and small resistance arteries. There is a good though incompletely characterized correlation between the expression of MYPT1 isoforms and sensitivity to NO/cGMPmediated relaxation, making this alternative splicing event an excellent model for the study of smooth muscle phenotypic diversity in relation to vascular function.
Highlights
Nitric oxide signaling through the cGMP kinase activates Myosin Phosphatase (MP) leading to calcium de-sensitization of force production
As in the rat 1) Tra2b is expressed at higher levels in phasic smooth
* Correspondence: steven.fisher@case.edu 1Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA Full list of author information is available at the end of the article muscle of small arteries and intestines, where E23 is spliced as compared to tonic smooth muscle of large vessels, where E23 is skipped
Summary
Nitric oxide signaling through the cGMP kinase (cGK1a) activates Myosin Phosphatase (MP) leading to calcium de-sensitization of force production. Results In a previous study we identified Transformer (Tra2b), a master regulator of splicing and sex determination in Drosophila, as a candidate tissue-specific regulator of MYPT1 E23 splicing [3].
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