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. 2021 Dec 30;12:790441. doi: 10.3389/fendo.2021.790441

Figure 1.

Figure 1

Phosphatidylinositol kinases involved in the generation of PI4P, PI (4,5)P2, and PI (3,4,5)P3 and kinase inhibitors used in this study. (A) Inhibition of PIKs by drugs; braces and arrows indicate the enzymes inhibited by inhibitors (blue text). Wortmannin (Wm), a fungal metabolite, is a cell-permeable, irreversible inhibitor of phosphatidylinositol-4-kinases PI4KA and PI4KB in a micromolar concentration range (20) and phosphadidylinositol-3-kinases (PI3Ks) in a nanomolar concentration range (29). PI3KCs are also inhibited by LY294002 in a micromolar concentration range (30). PI4KA is inhibited by GSK-A1 (25) and PI4KB by PIK93 (31), both in a nanomolar concentration range. ISA2011B blocks PIP5K1A (26), whereas UNC3230 inhibits PIP5K1C (27). If not otherwise indicated, we used 10 µM Wm, 100 nM GSK-A1, 100 nM PIK93, 10 µM ISA2011B, 1 µM UNC3230, and 1 and 50 µM LY2394002. Enzymes involved in PI5P production, PIKfyve, a FYVE finger-containing PIK, and PI5P-dependent PI (4,5)P2 production, PIP4K2, phosphatidylinositol-5-phosphate 4-kinases type-2, and their inhibitors, are not shown. (B, C) The expression pattern of PIK genes in scRNAseq of freshly dispersed rat pituitary cells. Uniform manifold approximation and projection (UMAP) plots showing the expression of P4ka and Pi4kb (B) and Pi4k2a and Pi4k2b (C) in pituitary cells: L, lactotrophs; G, gonadotrophs; T, thyrotrophs; S, somatotrophs; C, corticotrophs; M, melanotrophs; FS, folliculostellate cells; Pe, pericytes; Pc, pituicytes; and EC, endothelial cells. (D), Cell-type-specific expression of Pip5k1a-c (top panel); Pikfyve, Pip4k2a, Pip4k2c (middle panel); Pik3ca, Pik3r1, Pik3r2, and Pik3r3 (bottom panel), shown as mean expression level (color code) and percentage of pituitary cell types expressing these genes (area of circles).