TY - JOUR TI - STK25 suppresses Hippo signaling by regulating SAV1-STRIPAK antagonism AU - Bae, Sung Jun AU - Ni, Lisheng AU - Luo, Xuelian A2 - Cole, Philip A A2 - Weis, William I VL - 9 PY - 2020 DA - 2020/04/15 SP - e54863 C1 - eLife 2020;9:e54863 DO - 10.7554/eLife.54863 UR - https://doi.org/10.7554/eLife.54863 AB - The MST-LATS kinase cascade is central to the Hippo pathway that controls tissue homeostasis, development, and organ size. The PP2A complex STRIPAKSLMAP blocks MST1/2 activation. The GCKIII family kinases associate with STRIPAK, but the functions of these phosphatase-associated kinases remain elusive. We previously showed that the scaffolding protein SAV1 promotes Hippo signaling by counteracting STRIPAK (Bae et al., 2017). Here, we show that the GCKIII kinase STK25 promotes STRIPAK-mediated inhibition of MST2 in human cells. Depletion of STK25 enhances MST2 activation without affecting the integrity of STRIPAKSLMAP. STK25 directly phosphorylates SAV1 and diminishes the ability of SAV1 to inhibit STRIPAK. Thus, STK25 as the kinase component of STRIPAK can inhibit the function of the STRIPAK inhibitor SAV1. This mutual antagonism between STRIPAK and SAV1 controls the initiation of Hippo signaling. KW - human 293FT cell KW - human 293A cell KW - Escherichia coli JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -