Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Deletion of the protein kinase A/protein kinase G target SMTNL1 promotes an exercise-adapted phenotype in vascular smooth muscle.

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, contractile 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.

Pubmed ID: 18310078


  • Wooldridge AA
  • Fortner CN
  • Lontay B
  • Akimoto T
  • Neppl RL
  • Facemire C
  • Datto MB
  • Kwon A
  • McCook E
  • Li P
  • Wang S
  • Thresher RJ
  • Miller SE
  • Perriard JC
  • Gavin TP
  • Hickner RC
  • Coffman TM
  • Somlyo AV
  • Yan Z
  • Haystead TA


The Journal of biological chemistry

Publication Data

April 25, 2008

Associated Grants

  • Agency: NHLBI NIH HHS, Id: 5 R01 HL078795-04
  • Agency: NIDDK NIH HHS, Id: DK065954-02
  • Agency: NIAMS NIH HHS, Id: R01 AR050429

Mesh Terms

  • Animals
  • Cyclic AMP-Dependent Protein Kinases
  • Cyclic GMP-Dependent Protein Kinases
  • Female
  • Gene Deletion
  • Humans
  • Mice
  • Models, Biological
  • Muscle Fibers, Skeletal
  • Muscle Proteins
  • Muscle, Smooth, Vascular
  • Myosins
  • Phenotype
  • Phosphoproteins
  • Phosphorylation
  • Physical Conditioning, Animal