Tissue-specific regulation of S6K1 by insulin in chickens divergently selected for growth

Abstract In chickens, insulin injection leads to the activation of the early steps of insulin receptor signaling in liver but not in muscles. Paradoxically, muscle p70 S6 kinase (S6K1), a kinase controlling protein synthesis and growth, was markedly activated in response to insulin. The aim of this study was to further investigate S6K1 regulation and activation using chickens divergently selected for growth, i.e. fast- (FGL) and slow- (SGL) growing lines. In the Pectoralis major muscle, insulin stimulated S6K1 phosphorylation on T389 in FGL and SGL chickens, whereas S6K1 phosphorylation on T421/S424 was increased by insulin only in FGL chickens. Moreover, insulin-related increase in muscle S6K1 activity was greater in FGL chickens than in SGL chickens. Surprisingly, liver S6K1 was insulin insensitive in the two genotypes. Such difference of regulation between tissues and between genotypes was not observed for the protein kinase B, which is involved in insulin signaling upstream of S6K1, or for eukaryotic initiation factor 4E-binding protein. Interestingly, insulin-activated a S6K1 downstream target, the ribosomal protein S6, irrespective of tissue, suggesting that a pathway different of the S6K1 cascade may be involved in S6 phosphorylation in chicken liver. In conclusion, the regulation of S6K1 differs between the liver and muscle and between chickens divergently selected for growth. Our results suggest a potential involvement of S6K1 in the control of muscle growth and an open issue concerning S6K1 function in chicken liver.