Alteration in phosphorylation of P20 is associated with insulin resistance.
We have recently identified a small phosphoprotein, P20, as a common intracellular target for insulin and several of its antagonists, including amylin, epinephrine, and calcitonin gene-related peptide. These hormones elicit phosphorylation of P20 at its different sites, producing three phosphorylated isoforms: S1 with an isoelectric point (pI) value of 6.0, S2 with a pI value of 5.9, and S3 with a pI value of 5.6 (FEBS Letters 457:149-152 and 462:25-30, 1999). In the current study, we showed that P20 is one of the most abundant phosphoproteins in rat extensor digitorum longus (EDL) muscle. Insulin and amylin antagonize each other's actions in the phosphorylation of this protein in rat EDL muscle. Insulin inhibits amylin-evoked phosphorylation of S2 and S3, whereas amylin decreases insulin-induced phosphorylation of S1. In rats made insulin resistant by dexamethasone treatment, levels of the phosphoisoforms S2 and S3, which were barely detectable in healthy rats in the absence of hormone stimulation, were significantly increased. Moreover, the ability of insulin to inhibit amylin-evoked phosphorylation of these two isoforms was greatly attenuated. These results suggested that alterations in the phosphorylation of P20 might be associated with insulin resistance and that P20 could serve as a useful marker to dissect the cellular mechanisms of this disease.
Wang
Y
Y
School of Biological Sciences, University of Auckland, Auckland, New Zealand.
Xu
A
A
Ye
J
J
Kraegen
E W
EW
Tse
C A
CA
Cooper
G J
GJ
D000273:Adipose Tissue / Q000378:metabolism; D000682:Amyloid / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D004041:Dietary Fats / Q000494:pharmacology; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D004837:Epinephrine / Q000494:pharmacology; D050886:HSP20 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D058228:Islet Amyloid Polypeptide; D008099:Liver / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D009124:Muscle Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism; D012016:Reference Values; D014162:Transfection
D000682:Amyloid; D004041:Dietary Fats; D050886:HSP20 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D009124:Muscle Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; C087458:Hspb6 protein, rat; D003907:Dexamethasone; D015740:Calcitonin Gene-Related Peptide; D004837:Epinephrine