Transformer (Tra2β): master regulator of myosin phosphatase alternative splicing and smooth muscle responses to NO/cGMP signaling
نویسندگان
چکیده
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.
منابع مشابه
TRA2β controls Mypt1 exon 24 splicing in the developmental maturation of mouse mesenteric artery smooth muscle.
Diversity of smooth muscle within the vascular system is generated by alternative splicing of exons, yet there is limited understanding of its timing or control mechanisms. We examined splicing of myosin phosphatase regulatory subunit (Mypt1) exon 24 (E24) in relation to smooth muscle myosin heavy chain (Smmhc) and smoothelin (Smtn) alternative exons (Smmhc E6 and Smtn E20) during maturation of...
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