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-di mensional gel electrophoresis, We found that phosphorylation of three isoel ectric variants of P20 (termed ARPP1, ARPP2 and ARPP3) was associated with amylin's actions in rat skeletal muscle. Amylin decreased phosphorylation o f ARPP1 and increased phosphorylation of ARPP2 and ARPP3 in a dose-dependen t manner. Insulin inhibited amylin-evoked phosphorylation of ARPP2 and ARPP 3, The amylin-selective antagonist rat amylin-(8-37) completely reversed am ylin's action on ARPP3 and partially decreased phosphorylation of ARPP2, By contrast, the CGRP-selective antagonist, human CGRP-(8-37) blocked phospho rylation of ARPP2 but had little effect on ARPP3, These results suggest tha t amylin modifies phosphorylation of P20 via two independent mechanisms, an d that P20 might be a molecule mediating amylin's biological functions. (C) 1999 Federation of European Biochemical Societies.