Temporal coding of insulin action through multiplexing of the AKT pathway.
One of the unique characteristics of cellular signaling pathways is that a common signaling pathway can selectively regulate multiple cellular functions of a hormone; however, this selective downstream control through a common signaling pathway is poorly understood. Here we show that the insulin-dependent AKT pathway uses temporal patterns multiplexing for selective regulation of downstream molecules. Pulse and sustained insulin stimulations were simultaneously encoded into transient and sustained AKT phosphorylation, respectively. The downstream molecules, including ribosomal protein S6 kinase (S6K), glucose-6-phosphatase (G6Pase), and glycogen synthase kinase-3β (GSK3β) selectively decoded transient, sustained, and both transient and sustained AKT phosphorylation, respectively. Selective downstream decoding is mediated by the molecules' network structures and kinetics. Our results demonstrate that the AKT pathway can multiplex distinct patterns of blood insulin, such as pulse-like additional and sustained-like basal secretions, and the downstream molecules selectively decode secretion patterns of insulin.
Department of Biophysics, Graduate School of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan. kubota@bi.s.u-tokyo.ac.jp
Hiroyuki
H
Kubota
Rei
R
Noguchi
Yu
Y
Toyoshima
Yu-Ichi
Y
Ozaki
Shinsuke
S
Uda
Kanako
K
Watanabe
Wataru
W
Ogawa
Shinya
S
Kuroda
D000818:Animals; D002478:Cells, Cultured; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D007328:Insulin / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction
D007328:Insulin; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D038362:Glycogen Synthase Kinase 3; D005952:Glucose-6-Phosphatase