TY - JOUR

T1 - Contraction regulation of Akt in rat skeletal muscle

AU - Sakamoto, Kei

AU - Hirshman, Michael F.

AU - Aschenbach, William G.

AU - Goodyear, Laurie J.

PY - 2002/4/5

Y1 - 2002/4/5

N2 - The protein serine/threonine kinase Akt/protein kinase B has been recognized as a critical signaling mediator for multiple cell systems. The function of Akt in skeletal muscle is not well understood, and whether contractile activity stimulates Akt activity has been controversial. In the current study, contraction in situ, induced via sciatic nerve stimulation, significantly increased Akt Ser473 phosphorylation in multiple muscle types including the extensor digitorum longus (13-fold over basal), plantaris (5.8-fold), red gastrocnemius (4.7-fold), white gastrocnemius (3.3-fold), and soleus (1.6-fold). In addition to increasing phosphorylation, contraction in situ significantly increased the activity of all three Akt isoforms (Akt1 > Akt2 > Akt3) with maximal activation occurring at 2.5 min and returning to base line with 15 min of contraction. Akt phosphorylation and activity were also increased when isolated muscles were contracted in vitro in the absence of systemic factors, although to a much lesser extent. The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 fully inhibited contraction-stimulated Akt phosphorylation and activity but did not diminish contraction-stimulated glycogen synthase kinase-3 phosphorylation and glycogen synthase activity. These results demonstrate that contraction increases Akt phosphorylation and activity in skeletal muscle and that this stimulation is rapid, transient, muscle fiber type-specific, and wortmannin- and LY294002-inhibitable. Akt signaling is not necessary for the regulation of glycogen synthase activity in contracting skeletal muscle.

AB - The protein serine/threonine kinase Akt/protein kinase B has been recognized as a critical signaling mediator for multiple cell systems. The function of Akt in skeletal muscle is not well understood, and whether contractile activity stimulates Akt activity has been controversial. In the current study, contraction in situ, induced via sciatic nerve stimulation, significantly increased Akt Ser473 phosphorylation in multiple muscle types including the extensor digitorum longus (13-fold over basal), plantaris (5.8-fold), red gastrocnemius (4.7-fold), white gastrocnemius (3.3-fold), and soleus (1.6-fold). In addition to increasing phosphorylation, contraction in situ significantly increased the activity of all three Akt isoforms (Akt1 > Akt2 > Akt3) with maximal activation occurring at 2.5 min and returning to base line with 15 min of contraction. Akt phosphorylation and activity were also increased when isolated muscles were contracted in vitro in the absence of systemic factors, although to a much lesser extent. The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 fully inhibited contraction-stimulated Akt phosphorylation and activity but did not diminish contraction-stimulated glycogen synthase kinase-3 phosphorylation and glycogen synthase activity. These results demonstrate that contraction increases Akt phosphorylation and activity in skeletal muscle and that this stimulation is rapid, transient, muscle fiber type-specific, and wortmannin- and LY294002-inhibitable. Akt signaling is not necessary for the regulation of glycogen synthase activity in contracting skeletal muscle.

UR - http://www.scopus.com/inward/record.url?scp=0037023777&partnerID=8YFLogxK

U2 - 10.1074/jbc.M112410200

DO - 10.1074/jbc.M112410200

M3 - Journal article

C2 - 11809761

AN - SCOPUS:0037023777

VL - 277

SP - 11910

EP - 11917

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 14

ER -