Regulation of 130kDa smooth muscle myosin light chain kinase expression by an intronic CArG element
dc.contributor.author | Chen, Meng | |
dc.contributor.author | Zhang, Wenwu | |
dc.contributor.author | Lu, Xiao | |
dc.contributor.author | Hoggatt, April M. | |
dc.contributor.author | Gunst, Susan J. | |
dc.contributor.author | Kassab, Ghassan S. | |
dc.contributor.author | Tune, Johnathan D. | |
dc.contributor.author | Herring, B. Paul | |
dc.contributor.department | Department of Cellular & Integrative Physiology, IU School of Medicine | en_US |
dc.date.accessioned | 2015-09-17T15:22:30Z | |
dc.date.available | 2015-09-17T15:22:30Z | |
dc.date.issued | 2013 | |
dc.description.abstract | The mylk1 gene encodes a 220-kDa nonmuscle myosin light chain kinase (MLCK), a 130-kDa smooth muscle MLCK (smMLCK), as well as the non-catalytic product telokin. Together, these proteins play critical roles in regulating smooth muscle contractility. Changes in their expression are associated with many pathological conditions; thus, it is important to understand the mechanisms regulating expression of mylk1 gene transcripts. Previously, we reported a highly conserved CArG box, which binds serum response factor, in intron 15 of mylk1. Because this CArG element is near the promoter that drives transcription of the 130-kDa smMLCK, we examined its role in regulating expression of this transcript. Results show that deletion of the intronic CArG region from a β-galactosidase reporter gene abolished transgene expression in mice in vivo. Deletion of the CArG region from the endogenous mylk1 gene, specifically in smooth muscle cells, decreased expression of the 130-kDa smMLCK by 40% without affecting expression of the 220-kDa MLCK or telokin. This reduction in 130-kDa smMLCK expression resulted in decreased phosphorylation of myosin light chains, attenuated smooth muscle contractility, and a 24% decrease in small intestine length that was associated with a significant reduction of Ki67-positive smooth muscle cells. Overall, these data show that the CArG element in intron 15 of the mylk1 gene is necessary for maximal expression of the 130-kDa smMLCK and that the 130-kDa smMLCK isoform is specifically required to regulate smooth muscle contractility and small intestine smooth muscle cell proliferation. | en_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Chen, M., Zhang, W., Lu, X., Hoggatt, A. M., Gunst, S. J., Kassab, G. S., ... & Herring, B. P. (2013). Regulation of 130-kDa smooth muscle myosin light chain kinase expression by an intronic CArG element. Journal of Biological Chemistry, 288(48), 34647-34657. | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/6977 | |
dc.language.iso | en_US | en_US |
dc.relation.isversionof | 10.1074/jbc.M113.510362 | en_US |
dc.relation.journal | Journal of Biological Chemistry | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | Publisher | en_US |
dc.subject | Calcium Calmodulin-dependent Protein Kinase (CaMK) | en_US |
dc.subject | contractile protein | en_US |
dc.subject | intestine | en_US |
dc.title | Regulation of 130kDa smooth muscle myosin light chain kinase expression by an intronic CArG element | en_US |
dc.type | Article | en_US |