Proteasome-dependent decrease in Akt by growth factors in vascular smooth muscle cells.
Akt is activated by growth factors to regulate various aspects of vascular smooth muscle cell function. Platelet-derived growth factor (PDGF) and insulin-like growth factor-1 activated Akt in vascular smooth muscle cells with a rapid reduction of total Akt protein that lasted for several hours. The downregulation of Akt required phosphatidylinositol 3-kinase activity, but not intrinsic Akt activity. The downregulation of Akt was abrogated by MG-132, a proteasome inhibitor, but not by inhibitors of calpain or cathepsins. Akt was found in ubiquitin immune complex after PDGF treatment. Proteasome-dependent degradation of Akt may provide a counter-regulatory mechanism against overactivation of Akt.
Adachi
Mayumi
M
Department of Molecular Cardiovascular Biology, Yamaguchi University School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi 755-8505, Japan.
Katsumura
Koichi Ricardo
KR
Fujii
Kozo
K
Kobayashi
Sei
S
Aoki
Hiroki
H
Matsuzaki
Masunori
M
D000818:Animals; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017208:Rats, Wistar
D003546:Cysteine Endopeptidases; D004791:Enzyme Inhibitors; D006133:Growth Substances; D007334:Insulin-Like Growth Factor I; D009097:Multienzyme Complexes; D019869:Phosphatidylinositol 3-Kinases; D010982:Platelet-Derived Growth Factor; D046988:Proteasome Endopeptidase Complex; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C494920:Akt1 protein, rat