Fig. 4: GP73 induces drastic remodeling of the PKA kinase hub.
From: GP73 is a glucogenic hormone contributing to SARS-CoV-2-induced hyperglycemia
a, Overlapping numbers of significantly upregulated phosphopeptides and downregulated phosphopeptides in PMHs treated with rmGP73 (64 nM) or glucagon (3 μM) for 1 h. Localization probability ≥0.75 and fold-change ≥1.5 or fold-change ≤0.67 were declared significant. Significantly regulated phosphopeptides by GP73 are shown in blue and those regulated by glucagon are shown in red. b, Heat map of the top 30 highly upregulated phosphosites in PMHs treated with rmGP73. c, Network analysis of proteins involved in the glucogenesis signaling pathway in PMHs treated with rmGP73. Each of the phosphosites is color-coded based on fold change. Circular shapes show each protein that is upregulated in GP73-treated cells compared to PBS-treated cells. Lines indicate protein–protein interactions curated from databases of experimentally defined kinase–substrate relationships (STRING, confidence >0.7). d,e, Specific kinase–substrate motifs (d) or distribution of matching kinases (e) according to the phosphoproteomics data from the rmGP73-treated sample (P < 0.05) using MoMo (https://meme-suite.org/tools/momo) and Kinase Enrichment Analysis 2 (KEA2) based on one-tailed Fisher’s exact test. f, KEGG enriched pathway analysis of significantly regulated phosphopeptides in PMHs treated with rmGP73 (P < 0.05) using DAVID Bioinformatics Resources 6.8. mTOR, Mammalian target of rapamycin; FoxO, Forkhead Box O; VEGF, Vascular endothelial growth factor; ErbB, Epidermal growth factor family of receptor tyrosine kinases; GnRH, Gonadotropin-releasing hormone. The bar plot shows significantly dysregulated pathways and one-tailed Fisher’s exact test P values are shown on the x axis.
