A protein kinase B-dependent and rapamycin-sensitive pathway controls skeletal muscle growth but not fiber type specification

• DOI: 10.1073/pnas.142166599
• Publication Date: 2002-07-28T22:26:28Z
• Authors: Giorgia Pallafacc...; Elisa Calabria; Antonio L. Serrano; John M. Kalhovde; Stefano Schiaffino
• Keywords: ITGA7

Nerve activity controls fiber size and type in skeletal muscle, but the underlying molecular mechanisms remain largely unknown. We have previously shown that Ras–mitogen-activated protein kinase calcineurin control not regenerating rat muscle. Here we report constitutively active B (PKB), also known as Akt, increases prevents denervation atrophy adult muscles does affect profile. The coexistence of hypertrophic muscle fibers overexpressing activated PKB with normal-size untransfected within same points to a cell-autonomous growth by PKB. physiological role this pathway is confirmed finding phosphorylation status are significantly increased innervated compared denervated parallel growth. Muscle hypertrophy induced Ras double mutant (RasV12C40) activates selectively phosphoinositide 3-kinase–PKB completely blocked rapamycin, showing mammalian target rapamycin major downstream effector size. On other hand, nerve activity-dependent only partially inhibited dominant negative suggesting nerve-dependent signaling pathways involved present results support notion regulated through different mechanisms.