A) Small scale RNAi screen on downstream substrates of LKB1 in 293T STBS-luc cells. Error bars represent ± SD from triplicate samples. B, C) Nuclear Yap accumulation and decreases in Lats and Yap phosphorylation following knockdown of MARKs. D) Suppression of LKB1-driven cytoplasmic translocation of YAP following MARK4 knockdown in Dox-treated W4 cells. Scale bars, 20 µm. E) Confocal immunofluorescent and Z-stack analysis for Scribble (SCRIB, green), F-actin (red) and nuclei (blue) in LKB1 and MARKs knockdown in MCF7 cells. Note mislocalization of SCRIB following LKB1 or MARKs silencing. F) Immunofluorescence in W4 cells demonstrates that LKB1 activation leads to SCRIB re-localization to the cell membrane and actin cap and require MARK expression. G) Knockdown of SCRIB in 293T cells reduces S127 Yap phosphorylation. H) Knockdown of SCRIB in Dox-induced LKB1 activated W4 cells suppressed YAP re-localization to the cytoplasm/actin cap. Scale bars, 20 µm. I) Endogenous co-immunoprecipitation of MARK1 demonstrates biochemical interactions with LKB1, SCRIB, MST1 and LATS1. J) Immunoblot for MST1 and LATS1, in SCRIB immunopreciptates derived from 293T cells with concomitant knockdown of MARK1. Adjusted lysate amounts were used for the IP to obtain equal levels of immunoprecipitated SCRIB. K) Diagram showing LKB1/MARK signaling axis controlling SCRIB localization and MST/LATS activation.