Mitogen‐activated protein kinase‐activated protein kinase 2 (MK2) in skeletal muscle atrophy and hypertrophy

Abstract

Skeletal muscle is a highly plastic tissue. Overall muscle growth (hypertrophy) or muscle wasting (atrophy) results from alterations in intracellular signaling pathways with important regulatory steps occurring in the nucleus as well as in the cytoplasm. Previous studies have identified components of the Akt/mTor pathway as well as the p38 MAPK pathway as important for skeletal muscle hypertrophy and/or atrophy. The present study tests the hypothesis that MK2, a substrate of p38 which following phosphorylation, can be exported from the nucleus in a complex with p38, may be important for skeletal muscle growth. The expression of MK2 was examined in denervated mouse hind-limb (atrophic) and hemidiaphragm (transiently hypertrophic) muscles. MK2 mRNA expression decreased after denervation in both atrophic (48% of innervated controls, P < 0.001) and hypertrophic muscle (34% of innervated controls, P < 0.01) but MK2 protein expression decreased only in atrophic muscle (32% of innervated controls, P < 0.01). The level of T205 phosphorylated MK2 increased after denervation in both atrophic (fourfold increase, P < 0.01) and hypertrophic muscles (almost sevenfold increase, P < 0.001) whereas the level of T317 phosphorylated MK2 (necessary for nuclear export) increased after denervation in hypertrophic muscle (nearly threefold increase, P < 0.001) but not in atrophic muscle. Logarithmically transformed relative changes in MK2 phosphorylated at T317 correlated well (r(2) = 0.7737) with relative changes in muscle weight. The results suggest a role for MK2 in the regulation of muscle mass, a role which, at least in part, may be related to determining the subcellular localization of p38 in muscle fibers.

p38 mitogen-activated protein kinase and mitogen-activated protein kinase-activated protein kinase 2 (MK2) signaling in atrophic and hypertrophic denervated mouse skeletal muscle

“…The present study confirms previous observations [48] of increased MK2 T205 phosphorylation in denervated skeletal muscle and a differential response of MK2 T317 phosphorylation to denervation in hemidiaphragm (hypertrophic, increased T317 phosphorylation) and anterior tibial muscle (atrophic, decreased T317 phosphorylation). The present study also shows increased MK2 T205 phosphorylation and decreased T317 phosphorylation in denervated atrophic pooled gastrocnemius and soleus muscles.…”

“…Denervation of skeletal muscles generally causes atrophy of the muscles but the hemidiaphragm becomes transiently hypertrophic following denervation [45-48]. We have previously shown that the MK2 phosphorylation on T317 correlates with muscle weight in denervated atrophic anterior tibial muscle, denervated hypertrophic hemidiaphragm muscle and innervated control muscles [48].…”

“…We have previously shown that the MK2 phosphorylation on T317 correlates with muscle weight in denervated atrophic anterior tibial muscle, denervated hypertrophic hemidiaphragm muscle and innervated control muscles [48]. Since the T317 phosphorylation is likely to be important for nuclear export of MK2, possibly in complex with p38, the previous study suggested that in hypertrophic denervated muscle MK2 and/or p38 may be localized mainly in the cytoplasm whereas in denervated atrophic muscle they may be localized in the nucleus to a larger extent.…”

Effects of time of day on resistance exercise-induced anabolic signaling in skeletal muscle

“…p38 MAPK is responding to both anabolic (e.g., muscle cell stretch, functional overload) and catabolic stimuli (e.g., tumor necrosis factor α) (21,27,44). In the present study, phosphorylated p38 MAPK was elevated after the resistance loading in line with previous reports in humans (4,19,39,41).…”

Normal muscle structure, growth, development, and regeneration

“…From a simple point of view, skeletal muscle growth or hypertrophy and muscle wasting or atrophy result both from complex changes in intracellular signaling pathways in the nucleus and cytoplasm, involving the components of the Akt/mTor and the p38 MAPK pathways. MK2 (mitogen-activated protein kinase-activated protein kinase 2) participates in the regulation of muscle mass and determines the subcellular localization of p38 in muscle fibers, being phosphorylated and both exported from the nucleus in a complex with p38, involved with skeletal muscle growth [22].…”