Amylin evokes phosphorylation of P20 in rat skeletal muscle.
To investigate the signal transduction events underlying amylin's actions, the amylin-evoked protein phosphorylation cascade was analysed using two-dimensional gel electrophoresis. We found that phosphorylation of three isoelectric variants of P20 (termed ARPP1, ARPP2 and ARPP3) was associated with amylin's actions in rat skeletal muscle. Amylin decreased phosphorylation of ARPP1 and increased phosphorylation of ARPP2 and ARPP3 in a dose-dependent manner. Insulin inhibited amylin-evoked phosphorylation of ARPP2 and ARPP3. The amylin-selective antagonist rat amylin-(8-37) completely reversed amylin's action on ARPP3 and partially decreased phosphorylation of ARPP2. By contrast, the CGRP-selective antagonist, human CGRP-(8-37) blocked phosphorylation of ARPP2 but had little effect on ARPP3. These results suggest that amylin modifies phosphorylation of P20 via two independent mechanisms, and that P20 might be a molecule mediating amylin's biological functions.
Wang
Y
Y
School of Biological Sciences, University of Auckland, New Zealand.
Xu
A
A
Cooper
G J
GJ
D000682:Amyloid / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D050886:HSP20 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D006614:Hindlimb / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D058228:Islet Amyloid Polypeptide; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism* / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
D000682:Amyloid; D050886:HSP20 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D009124:Muscle Proteins; C087458:Hspb6 protein, rat