Fig. 6: LAPTM5 suppressed activation of MAPK signaling pathway by promoting the lysosomal degradation of CDC42.

a Combined KEGG analysis results showing the most enriched MAPK pathway. b and c Western blot images (b) and quantitative results (c) of phosphorylated and total protein levels of p38, JNK1/2, and ERK1/2 in mice livers of indicated groups (n = 3 mice/group). Data represent mean ± SD, two-tailed Student’s t-test was used to evaluate differences. d and e Western blot images showing phosphorylated and total protein levels of p38, JNK1/2, and ERK1/2 in the cells from the indicated group. f Scheme of identifying the protein interacting with LAPTM5 by analyzing IP-MS. g and h Co-IP (g) and GST pull-down (h) shows the interaction between LAPTM5 and CDC42. i Co-IP assays for examining the difference in binding strength between LAPTM5 and CDC42 after the stimulation of PA. j and k Western blot results of exogenous (j) and endogenous (k) CDC42 expression after overexpression of different concentrations of LAPTM5. (l) Western blot images (up) and Quantitative analysis (down) of CDC42 expression in hepatocytes of LAPTM5-KO mice after PA stimulated (n = 3mice/group). Data represent mean ± SD, and one-way ANOVA of the Bonferroni post-hoc test was used to evaluate differences. m Western blot images of LAPTM5 and CDC42 expression in the group of NASH or non-NASH (n = 5 people/group). n Western blot result of exogenous CDC42 expression after LAPTM5 overexpression under Chlq or MG132 treatment. o Western blot images of exogenous CDC42 expression trend with LAPTM5 overexpression in a gradient under the treatment of Chlq. p Confocal microscopy images of the co-localization of LAMP1 (green) and CDC42 (red) in L02 cells in the indicated groups (Nuclei, blue). Scale bar, 8 μm (n = 3 independent experiments). PAOA, 0.5 mM/1.0 mM; PA, 0.5 mM, OA, 1.0 mM. Chlq, 50 μM; MG132, 50 μM. Immunoblots are representative of three independent experiments. Source data are provided as a Source data file.