Adenosine 3',5'-cyclic monophosphate-dependent protein kinase (A kinase) regulation of insulin receptor function: phosphorylation of insulin receptor with A kinase decreases the insulin binding activity.
The effect of phosphorylation of insulin receptor with adenosine 3',5'-cyclic monophosphate-dependent protein kinase (A kinase) on its insulin binding activity was investigated by using insulin receptors prepared from rat liver in vitro. A 95 KDa protein was phosphorylated by stimulation of insulin receptor kinase. This protein was also phosphorylated by A kinase. Analysis of phosphoamino acid showed that tyrosine residue(s) was phosphorylated by activation of insulin receptor kinase, whereas phosphoserine and phosphothreonine were dominantly generated by activation of A kinase. [125I] Iodoinsulin binding activity was decreased by prior phosphorylation of the receptor with A kinase. Scatchard analysis showed that the affinity for insulin was decreased by the phosphorylation with A kinase. Although the maximal activity of insulin receptor kinase was not affected by phosphorylation with A kinase, the insulin concentration which induced half maximal activity (ED50) of the receptor kinase was increased by the phosphorylation with A kinase. These results suggested that counter regulatory hormones whose actions are mediated by the generation of adenosine 3',5'-cyclic monophosphate regulate the insulin binding to the alpha subunit through phosphorylation of the beta subunit of insulin receptor.
Yamauchi
K
K
Department of Geriatrics, Endocrinology and Metabolism, Shinshu University School of Medicine, Matsumoto, Japan.
Hashizume
K
K
Ichikawa
K
K
Ohtsuka
H
H
Ohara
N
N
Miyamoto
T
T
Kobayashi
M
M
Yamada
T
T
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000032:analysis; D010766:Phosphorylation; D011233:Precipitin Tests; D011494:Protein Kinases / Q000502:physiology*; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism*
D007328:Insulin; D009943:Organophosphorus Compounds; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D011972:Receptor, Insulin