| First Author | Ferey JL | Year | 2014 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 307 |
| Issue | 8 | Pages | E686-94 |
| PubMed ID | 25159322 | Mgi Jnum | J:215561 |
| Mgi Id | MGI:5605625 | Doi | 10.1152/ajpendo.00322.2014 |
| Citation | Ferey JL, et al. (2014) Constitutive activation of CaMKKalpha signaling is sufficient but not necessary for mTORC1 activation and growth in mouse skeletal muscle. Am J Physiol Endocrinol Metab 307(8):E686-94 |
| abstractText | Skeletal muscle loading/overload stimulates the Ca(2+)-activated, serine/threonine kinase Ca(2+)/calmodulin-dependent protein kinase kinase-alpha (CaMKKalpha); yet to date, no studies have examined whether CaMKKalpha regulates muscle growth. The purpose of this study was to determine if constitutive activation of CaMKKalpha signaling could stimulate muscle growth and if so whether CaMKKalpha is essential for this process. CaMKKalpha signaling was selectively activated in mouse muscle via expression of a constitutively active form of CaMKKalpha using in vivo electroporation. After 2 wk, constitutively active CaMKKalpha expression increased muscle weight ( approximately 10%) and protein content ( approximately 10%), demonstrating that activation of CaMKKalpha signaling can stimulate muscle growth. To determine if active CaMKKalpha expression stimulated muscle growth via increased mammalian target of rapamycin complex 1 (mTORC1) signaling and protein synthesis, [(3)H]phenylalanine incorporation into proteins was assessed with or without the mTORC1 inhibitor rapamycin. Constitutively active CaMKKalpha increased protein synthesis approximately 60%, and this increase was prevented by rapamycin, demonstrating a critical role for mTORC1 in this process. To determine if CaMKKalpha is essential for growth, muscles from CaMKKalpha knockout mice were stimulated to hypertrophy via unilateral ablation of synergist muscles (overload). Surprisingly, compared with wild-type mice, muscles from CaMKKalpha knockout mice exhibited greater growth ( approximately 15%) and phosphorylation of the mTORC1 substrate 70-kDa ribosomal protein S6 kinase (Thr(389); approximately 50%), demonstrating that CaMKKalpha is not essential for overload-induced mTORC1 activation or muscle growth. Collectively, these results demonstrate that activation of CaMKKalpha signaling is sufficient but not necessary for activation of mTORC1 signaling and growth in mouse skeletal muscle. |
