Steroid resistance induced by wild-type or mutant IL7R signaling molecules is associated with activation of MEK-ERK and/or AKT.

<p>(A) Western blot results for total and/or phosphorylated levels of IL7R signaling molecules following doxycycline induction (+Dox) of wild-type or mutant forms of IL7R, JAK1, JAK3, NRAS, or AKT molecules in SUPT1 cells. The steroid-sensitive and -resistant panels are indicated. Cellular lysate of parental SUPT1 cells was used as a control. (B–G) β-actin-normalized protein concentrations for (B) NR3C1, (C) pMEK, (D) pERK, (E) pAKT, (F) pGSK3B, and (G) BCLXL in doxycycline-induced steroid-sensitive and -resistant SUPT1 lines. Significance levels were calculated using the Mann-Whitney <i>U</i> test. In (E), phospho-AKT levels are shown for all lines except for lines induced to express construct-driven AKT and AKT^E17K. (H) Schematic overview of crosstalk between the proapoptotic NR3C1 response following steroid exposure and activation of MEK-ERK and AKT pathways downstream of IL7R signaling mutations. Green vectors indicate molecules that drive a proapoptotic, steroid-sensitive response, whereas red vectors indicate molecules that drive an antiapoptotic, steroid-resistant response. See also <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1002200#pmed.1002200.s007" target="_blank">S7 Fig</a>.