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. 2021 Apr 1;16(4):868–882. doi: 10.1016/j.stemcr.2021.03.003

Figure 5.

Figure 5

CDK5 Activated P38MAPK via Src and Induced Differentiation of Pluripotent Stem Cells into Cardiomyocytes

(A) Phosphorylation levels of CDK5, Src, and P38MAPK in wild-type mouse ESCs (mESCs) and Lphn2-knockout (KO) mESCs treated with the respective inhibitors during cardiac differentiation, as detected by western blotting.

(B) Quantification of the phosphorylation ratios of CDK5, Src, and P38MAPK in wild-type mESCs (WT mESCs) and Lphn2-KO mESCs. Values are shown relative to the phosphorylation ratio for the vehicle group of WT mESCs on day 3 of differentiation. ∗p < 0.05, ∗∗p < 0.01, #not significant, one-way ANOVA and post hoc Bonferroni test; n = 3 independent replicates.

(C) Gene expression analysis of Mesp1, Isl1, Tbx5, and cTnT in WT mESCs and Lphn2-KO mESCs treated with inhibitors of CDK5, Src, and P38MAPK on day 7 of cardiac differentiation. Values are shown relative to the expression in WT mESCs on day 0. ∗∗p < 0.01, #not significant, one-way ANOVA and post hoc Bonferroni test; n = 3 independent replicates.

(D) Schematic illustration of the molecular mechanism of LPHN2-mediated cardiac differentiation via the CDK5-Src-P38MAPK signaling cascade.