title: Overexpression or ablation of JNK in skeletal muscle has no effect on glycogen synthase activity.
abstract: c-Jun NH(2)-terminal kinase (JNK) is highly expressed in skeletal muscle and is robustly activated in response to muscle contraction. Little is known about the biological functions of JNK signaling in terminally differentiated muscle cells, although this protein has been proposed to regulate insulin-stimulated glycogen synthase activity in mouse skeletal muscle. To determine whether JNK signaling regulates contraction-stimulated glycogen synthase activation, we applied an electroporation technique to induce JNK overexpression (O/E) in mouse skeletal muscle. Ten days after electroporation, in situ muscle contraction increased JNK activity 2.6-fold in control muscles and 15-fold in the JNK O/E muscles. Despite the enormous activation of JNK activity in JNK O/E muscles, contraction resulted in similar increases in glycogen synthase activity in control and JNK O/E muscles. Consistent with these findings, basal and contraction-induced glycogen synthase activity was normal in muscles of both JNK1- and JNK2-deficient mice. JNK overexpression in muscle resulted in significant alterations in the basal phosphorylation state of several signaling proteins, such as extracellular signal-regulated kinase 1/2, p90 S6 kinase, glycogen synthase kinase 3, protein kinase B/Akt, and p70 S6 kinase, in the absence of changes in the expression of these proteins. These data suggest that JNK signaling regulates the phosphorylation state of several kinases in skeletal muscle. JNK activation is unlikely to be the major mechanism by which contractile activity increases glycogen synthase activity in skeletal muscle.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Nobuharu
authors.initials: N
authors.lastname: Fujii
authors.forename: Marni D
authors.initials: MD
authors.lastname: Boppart
authors.forename: Scott D
authors.initials: SD
authors.lastname: Dufresne
authors.forename: Patricia F
authors.initials: PF
authors.lastname: Crowley
authors.forename: Alison C
authors.initials: AC
authors.lastname: Jozsi
authors.forename: Kei
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Haiyan
authors.initials: H
authors.lastname: Yu
authors.forename: Williams G
authors.initials: WG
authors.lastname: Aschenbach
authors.forename: Shokei
authors.initials: S
authors.lastname: Kim
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Miyazaki
authors.forename: Liangyou
authors.initials: L
authors.lastname: Rui
authors.forename: Morris F
authors.initials: MF
authors.lastname: White
authors.forename: Michael F
authors.initials: MF
authors.lastname: Hirshman
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Goodyear
mesh_terms: D000818:Animals; D015536:Down-Regulation; D018274:Electroporation; D004789:Enzyme Activation; D018014:Gene Transfer Techniques; D006006:Glycogen Synthase / Q000378:metabolism*; D006801:Humans; D007273:Injections, Intramuscular; D055504:Insulin Receptor Substrate Proteins; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D048055:Mitogen-Activated Protein Kinase 8; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D009119:Muscle Contraction / Q000502:physiology; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology / Q000502:physiology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D012694:Serine / Q000235:genetics; D014443:Tyrosine / Q000378:metabolism
chemical_list: C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D009124:Muscle Proteins; D010750:Phosphoproteins; D014443:Tyrosine; D012694:Serine; D006006:Glycogen Synthase; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases