Deletion of the Protein Kinase A/Protein Kinase G Target SMTNL1 Promotes an Exercise-adapted Phenotype in Vascular Smooth Muscle
dc.contributor.author | Wooldridge, Anne A. | en_US |
dc.contributor.author | Fortner, Christopher N. | en_US |
dc.contributor.author | Lontay, Beata | en_US |
dc.contributor.author | Akimoto, Takayuki | en_US |
dc.contributor.author | Neppl, Ronald L. | en_US |
dc.contributor.author | Facemire, Carie | en_US |
dc.contributor.author | Datto, Michael B. | en_US |
dc.contributor.author | Kwon, Ashley | en_US |
dc.contributor.author | McCook, Everett | en_US |
dc.contributor.author | Li, Ping | en_US |
dc.contributor.author | Wang, Shiliang | en_US |
dc.contributor.author | Thresher, Randy J. | en_US |
dc.contributor.author | Miller, Sara E. | en_US |
dc.contributor.author | Perriard, Jean-Claude | en_US |
dc.contributor.author | Gavin, Timothy Patrick | en_US |
dc.contributor.author | Hickner, Robert C. | en_US |
dc.contributor.author | Coffman, Thomas M. | en_US |
dc.contributor.author | Somlyo, Avril V. | en_US |
dc.contributor.author | Yan, Zhen | en_US |
dc.contributor.author | Haystead, Timothy A. J. | en_US |
dc.date.accessioned | 2011-04-28T19:18:29Z | en_US |
dc.date.accessioned | 2011-05-16T20:40:50Z | |
dc.date.available | 2011-04-28T19:18:29Z | en_US |
dc.date.available | 2011-05-16T20:40:50Z | |
dc.date.issued | 2008-04-25 | en_US |
dc.description.abstract | In vivo protein kinases A and G (PKA and PKG) coordinately phosphorylate a broad range of substrates to mediate their various physiological effects. The functions of many of these substrates have yet to be defined genetically. Herein we show a role for smoothelin-like protein 1 (SMTNL1), a novel in vivo target of PKG/PKA, in mediating vascular adaptations to exercise. Aortas from smtnl1-/- mice exhibited strikingly enhanced vasorelaxation before exercise, similar in extent to that achieved after endurance training of wild-type littermates. Additionally, con- tractile responses to alpha-adrenergic agonists were greatly attenuated. Immunological studies showed SMTNL1 is expressed in smooth muscle and type 2a striated muscle fibers. Consistent with a role in adaptations to exercise, smtnl1-/- mice also exhibited increased type 2a fibers before training and better performance after forced endurance training compared smtnl1+/+ mice. Furthermore, exercise was found to reduce expression of SMTNL1, particularly in female mice. In both muscle types, SMTNL1 is phosphorylated at Ser-301 in response to adrenergic signals. In vitro SMTNL1 suppresses myosin phosphatase activity through a substrate-directed effect, which is relieved by Ser- 301 phosphorylation. Our findings suggest roles for SMTNL1 in cGMP/cAMP-mediated adaptations to exercise through mechanisms involving direct modulation of contractile activity. Originally published Journal of Biological Chemistry, Vol. 283, No. 17, Apr 2008 | en_US |
dc.identifier.citation | Journal of Biological Chemistry; 283:17 p. 11850-11859 | en_US |
dc.identifier.doi | 10.1074/jbc.M708628200 | |
dc.identifier.pmid | PMC2431077 | en_US |
dc.identifier.uri | http://hdl.handle.net/10342/3427 | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | East Carolina University | en_US |
dc.relation.uri | http://www.jbc.org/content/283/17/11850.full.pdf+html | en_US |
dc.rights | Author notified of opt-out rights by Cammie Jennings prior to upload of this article. | en_US |
dc.subject | Exercise adapted phenotype | en_US |
dc.subject | Protein kinases | en_US |
dc.subject | Vascular smooth muscle | en_US |
dc.title | Deletion of the Protein Kinase A/Protein Kinase G Target SMTNL1 Promotes an Exercise-adapted Phenotype in Vascular Smooth Muscle | en_US |
dc.type | Article | en_US |
ecu.journal.issue | 17 | |
ecu.journal.name | Journal of Biological Chemistry | |
ecu.journal.pages | 11850-11859 | |
ecu.journal.volume | 283 |
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