Mitogen-activated protein kinase and p70 ribosomal protein S6 kinase are not involved in the insulin-dependent stimulation of cAMP phosphodiesterase kinase in rat adipocytes.
To elucidate the mechanism of anti-lipolytic action of insulin in rat epididymal adipocytes, we explored the potential mechanism that might be involved in the hormone-dependent stimulation of cAMP phosphodiesterase (PDE) kinase. PDE kinase was assayed in a cell-free system. Both wortmannin and LY294002, highly specific inhibitors of phosphatidylinositol 3-kinase, almost completely blocked the hormonal effect not only on PDE kinase but also on mitogen-activated protein (MAP) kinase. Neither PD98059, a specific inhibitor of MAP kinase, nor rapamycin, a potent inhibitor of insulin-dependent stimulation of p70 ribosomal protein S6 kinase (p70S6K), had inhibitory effect on that of PDE kinase. These results are consistent with the view that (i) insulin-activated PDE kinase as well as MAP kinase and p70S6K are localized downstream of phosphatidylinositol 3-kinase, (ii) PDE kinase is distinct from either MAP kinase or p70S6K and (iii) PDE kinase does not exist downstream of either MAP kinase or p70S6K. It is suggested that PDE kinase and MAP kinase or p70S6K may be localized in separate branches of the cascade of insulin action. The branching point of the cascade could be either at or below the level of phosphatidylinositol 3-kinase.
Onuma
H
H
Department of Laboratory Medicine, Ehime University School of Medicine, Japan.
Makino
H
H
Osawa
H
H
Suzuki
Y
Y
Taira
M
M
Kanatsuka
A
A
Saito
Y
Y
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology*; D000595:Amino Acid Sequence; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D002474:Cell-Free System; D002867:Chromones / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004822:Epididymis / Q000166:cytology; D005419:Flavonoids / Q000494:pharmacology; D015151:Immunoblotting; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011090:Polyenes / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019893:Ribosomal Protein S6 Kinases; D020123:Sirolimus; D000077191:Wortmannin
D000730:Androstadienes; D002867:Chromones; D005419:Flavonoids; D007328:Insulin; D009025:Morpholines; D011090:Polyenes; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D011494:Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; C111878:cAMP phosphodiesterase kinase; D019893:Ribosomal Protein S6 Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D020123:Sirolimus; D000077191:Wortmannin