| First Author | Yang Q | Year | 2001 |
| Journal | Cardiovasc Res | Volume | 51 |
| Issue | 1 | Pages | 80-8 |
| PubMed ID | 11399250 | Mgi Jnum | J:133394 |
| Mgi Id | MGI:3778363 | Doi | 10.1016/s0008-6363(01)00273-5 |
| Citation | Yang Q, et al. (2001) PKA-dependent phosphorylation of cardiac myosin binding protein C in transgenic mice. Cardiovasc Res 51(1):80-8 |
| abstractText | OBJECTIVE: To investigate the physiological role of cAMP-dependent protein kinase A (PKA)-mediated, cardiac myosin binding protein C (MyBP-C) phosphorylation. METHODS: A cardiac MyBP-C cDNA lacking nine amino acids, which contained a phosphorylation site, was made, and subsequently used to generate multiple lines of transgenic mice. Upon confirming that a partial replacement of endogenous protein with transgenic protein occurred, the biochemical and physiological consequences were studied. PKA-dependent phosphorylation assays were used to estimate the phosphorylation states of major cardiac PKA substrates. Myofibril Mg-ATPase activities were also measured. Isolated working heart and whole animal exercise studies were used to measure the physiological changes. RESULTS: Transgenic mice displayed a compensatory response, with PKA-mediated phosphorylation of both troponin I and phospholamban showing significant increases. The remaining endogenous cardiac MyBP-C also showed increased phosphorylation levels. Maximal Mg(2+)-ATPase activity was increased. Significant functional changes at both the whole organ and whole animal levels also occurred. Parameters reflecting cardiac contractility and relaxation increased about 22 and 25%, respectively, in the mutant relative to wild type mice (n=5, P<0.001). In young adults the capacity for stress exercise, quantitated using an exercise treadmill regimen, was substantially enhanced (n=6, P<0.01). CONCLUSIONS: Cardiac MyBP-C phosphorylation plays an important physiological role and that the protein's degree of phosphorylation is coordinated with the phosphorylation levels of other proteins within the contractile apparatus. |
