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Distinct Signaling Pathways Are Activated in Response to
Mechanical Stress Applied Axially and Transversely to Skeletal Muscle
Fibers*
Ashok
Kumar,
Imran
Chaudhry,
Michael B.
Reid, and
Aladin M.
Boriek
From the Department of Medicine, Baylor College of Medicine,
Houston, Texas 77030
In the diaphragm muscle we tested the hypothesis
that MAP kinase signaling pathways are activated by mechanical stress
andsuch signaling pathways are dependent on the direction in whichmechanical stress is applied. Although equal magnitudes of
mechanicalstress were applied axially and transversely a greater level
ofactivation of ERK1/2, p38, Raf-1, p90 RSK, Elk-1, and the DNAbinding activity of AP-1 transcription factor was produced whenthe
muscle was stretched transversely than when stretched axially.A
significant up-regulation in protein tyrosine phosphorylationwas
observed in axially or transversely loaded diaphragm musclesand the
activation of ERK1/2 was completely inhibited by genistein(protein-tyrosine kinase inhibitor). Pretreatment of muscles withwortmannin (phosphoinositide 3-kinase inhibitor), TMB-8 (antagonistof
intracellular calcium release), GF109203X (PKC inhibitor),or PD98059
(MEK1/2 inhibitor) blocked the activation of ERK1/2kinases in
response to axial but not to transverse loading. Onthe other hand,
pretreatment of muscles with protein kinase Ainhibitors H-7 and KT5720
completely suppressed the activationof ERK1/2 in response to
transverse loading only. Taken togetherwith the alterations of MAP
kinases and the findings of elevationsof downstream transcription
targets, our data are consistent withtwo distinct MAP kinase signal
transduction pathways in responseto mechanicalstress.
Sustained postexercise increases in AS160 Thr642 and Ser588 phosphorylation in skeletal muscle without sustained increases in kinase phosphorylation.
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