Zipper-interacting protein kinase induces Ca(2+)-free smooth muscle contraction via myosin light chain phosphorylation
Department of Physiology
Amino Acid Sequence; Animals; Apoptosis Regulatory Proteins; Base Sequence; Calcium; Calcium-Calmodulin-Dependent Protein Kinases; Enzyme Inhibitors; Gene Library; Gizzard; Humans; Kinetics; Leucine Zippers; Mesenteric Arteries; Mice; Microcystins; Molecular Sequence Data; Molecular Weight; Muscle Contraction; Muscle, Smooth; Muscle, Smooth, Vascular; Peptides, Cyclic; Phosphorylation; Phosphoserine; Phosphothreonine; Protein-Serine-Threonine Kinases; Rabbits; Rats; Recombinant Fusion Proteins; Sequence Alignment; Sequence Homology, Amino Acid
Life Sciences | Medicine and Health Sciences
The inhibition of myosin phosphatase evokes smooth muscle contraction in the absence of Ca(2+), yet the underlying mechanisms are not understood. To this end, we have cloned smooth muscle zipper-interacting protein (ZIP) kinase cDNA. ZIP kinase is present in various smooth muscle tissues including arteries. Triton X-100 skinning did not diminish ZIP kinase content, suggesting that ZIP kinase associates with the filamentous component in smooth muscle. Smooth muscle ZIP kinase phosphorylated smooth muscle myosin as well as the isolated 20-kDa myosin light chain in a Ca(2+)/calmodulin-independent manner. ZIP kinase phosphorylated myosin light chain at both Ser(19) and Thr(18) residues with the same rate constant. The actin-activated ATPase activity of myosin increased significantly following ZIP kinase-induced phosphorylation. Introduction of ZIP kinase into Triton X-100-permeabilized rabbit mesenteric artery provoked a Ca(2+)-free contraction. A protein phosphatase inhibitor, microcystin LR, also induced contraction in the absence of Ca(2+), which was accompanied by an increase in both mono- and diphosphorylation of myosin light chain. The observed sensitivity of the microcystin-induced contraction to various protein kinase inhibitors was identical to the sensitivity of isolated ZIP kinase to these inhibitors. These results suggest that ZIP kinase is responsible for Ca(2+) independent myosin phosphorylation and contraction in smooth muscle.
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Citation: J Biol Chem. 2001 Aug 3;276(31):29567-74. Epub 2001 May 30. Link to article on publisher's site
DOI of Published Version
The Journal of biological chemistry
Niiro, Naohisa and Ikebe, Mitsuo, "Zipper-interacting protein kinase induces Ca(2+)-free smooth muscle contraction via myosin light chain phosphorylation" (2001). Open Access Articles. 740.