TSC differentiation, stress, and mRNA and protein levels. TSC differentiation is affected by stress globally on the mRNA level and functionally on the protein level. The black lines show the mechanism where ID2 is lost and Hand1 derepressed to activate the PL1 promoter, the first marker of differentiation. Stress-induced PL1 protein requires the activity of SAPK which stabilizes and induces Hand1, and AMPK which induces proteasome-dependent ID2 loss [Zhong et al. submitted]. The dash-lined box shows that the kinetics of AMPK induction and ID2 loss, and AMPK-dependence of ID2 loss, are the same in E3.5 embryos and TSC. The solid lined boxes show that like differentiation-inhibiting ID2 protein, inhibitory ErrB mRNA is also downregulated by stress, like Hand1 protein, positively-acting STRA13, Gata2, and HES1 mRNA are upregulated by stress, and like PL1 hormone PLPM, proliferin, and PLPM hormone mRNA transcripts are also upregulated by stress [Liu et al. 2009]. These studies were carried out using hyperosmolar stress, but BaP also induces AMPK-dependent ID2 loss in TSC [Xie et al. (in press); Toft and Linzer 2000; Ma and Linzer 2000].