Activation of ribosomal protein S6 kinases does not increase glycogen synthesis or glucose transport in rat adipocytes.
Rat adipocytes were incubated with insulin or epidermal growth factor (EGF) before the mitogen-activated protein (MAP) kinases, ERK-1 and ERK-2, and the ribosomal protein S6 kinases, Rsk-2 and p70S6K, were resolved by ion exchange chromatography and identified by immunoblotting. EGF was more effective than insulin in increasing the activity of two kinases that reacted with Rsk-2 antibody (2- and 2.5-fold with EGF versus 1.6- and 1.2-fold with insulin). EGF was also more effective than insulin in increasing the activity of ERK-1 (5-fold versus 2-fold) and ERK-2 (2.5-fold versus 1.5 fold). The activity of p70S6K was increased by approximately the same extent by EGF and insulin (1.7-fold versus 2-fold). Rapamycin blocked activation of p70S6K by insulin, but it did not attenuate the effect (2-fold) of insulin on increasing the glycogen synthase activity ratio (+/-glucose-6-P). Insulin increased glucose incorporation into glycogen and 2-deoxyglucose uptake by approximately 5-fold, whereas EGF and phorbol 12-myristate were without effect. Thus, activation of MAP kinases and ribosomal protein S6 kinases appears insufficient to activate glycogen synthase or glucose transport, the two key components in the stimulation of glycogen synthesis by insulin.
Lin
T A
TA
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110.
Lawrence
J C
JC
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000096:biosynthesis*; D006006:Glycogen Synthase / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D011090:Polyenes / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019893:Ribosomal Protein S6 Kinases; D020123:Sirolimus; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007328:Insulin; D011090:Polyenes; D004815:Epidermal Growth Factor; D006003:Glycogen; D006006:Glycogen Synthase; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; D020123:Sirolimus