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

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]