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Table 3 MAPK pathway phosphorylation changes associated with mechanical perturbation and neuromuscular diseases in skeletal muscle

From: The ties that bind: functional clusters in limb-girdle muscular dystrophy

Pathway Disease Finding Citations
Jnk (Thr183/Tyr195) Healthy Jnk activation directly correlated to active tension but not passive tension. P54 is most sensitive [130]
Healthy Resistance exercise stimulates P-JNK [140]
DMD (mdx) Elevated P-JNK1 associated with pathology (all refs). JNK1 inhibition by JIP1 attenuates pathology; P54 > p46 in phosphorylation status; Murine diaphragm highest elevation [141]. p46 > p54 in phosphorylation status [142] [131, 141, 142]
p38 (Thr180/Tyr182) Healthy Phosphorylated p38 is not sensitive to tension [130]
LGMD2C (Sgcg−/−) Stretched myotubes have elevated p-p38 [143]
FSHD P38 inhibition reduces DUX4 expression [144]
LGMD2B (SJL) Reduction of P-p38 by paloxamer188 but no comparison to wildtype mice [145]
DMD (mdx) Loss of MKP5 improves phenotype [146]
LGMD2F (Sgcd−/−); DMD (mdx) Elevated p38 associated with pathology; transgenic ablation of p38a (mapk14) reduces pathology; [147]
LGMD2A (C3KO) Suppressed in sedentary and run conditions [148]
ERK1/2 (Thr202/Tyr204) Healthy Erk phosphorylation correlated with both active and passive tension [130]
DMD (mdx) Elevated in resting diaphragm, with stretch-dependent enhancement [149]
LGMD2C (Sgcg−/−) Stretched myotubes have elevated P-ERK1/2 [143]
LGMD2C (Sgcg−/−) Resting elevated P-ERK1/2 [133, 134]
LGMD2C (Sgcg−/−) Sustained levels with contraction but not passive stretch [131, 134]
DMD (mdx); LGMD2C (Sgcg−/−) Uncoupling of mechano-signaling. Elevated P-ERK1/2 in human biopsies of LGMD2C/2E and DMD [136]
LGMD2C Dusp6 (ERK phosphatase) genetic modifier [150]
LGMD2F (Sgcd−/−) Increased ERK1/2 protects against dystrophy with fast-to-slow fiber type shift; selective ablation of ERK1 [151]