Figure 3
Synergistic regulation of β-cell phosphoproteome mediated by GLP-1 and glucose at site level. (A) Heatmap showing the ratio condition B/A in three experiments for class 1 sites regulated by HGLP1 with high confidence. These phosphorylation sites were classified into 5 categories as defined in Fig. 1G. Synergistic-regulated sites with their biological functions reported are listed, together with their reported kinases. (B) Histogram of the ratio difference rate occurrences showing whether GLP-1 and glucose induced phosphorylation change of each site in an additive manner. All HGLP1 high confidence regulated sites were used for calculation. Ratio difference rate from additive effect was defined in Supplementary Fig. S4. (C) Activation of kinases mediated by GLP-1 (LGLP1), glucose (HGlc) or their synergism (HGLP1) according to the phosphorylation status of their substrates predicted by NetworKIN algorithm. Only both-regulated sites mediated by GLP-1 and glucose were used for kinase activation calculation. Phosphorylation status of each site according to each treatment were divided by ratio_additive as defined in Supplemental Fig. S4. Paired Student’s t-test for each site was applied to calculate the significance of activation status of their predicted kinase. ns, non-significant. *p < 0.05; **p < 0.01 (paired Student’s t test). Data were represented in mean ± SEM. n stands for the number of predicted substrates of each kinase.
