STK25 suppresses Hippo signaling by regulating SAV1-STRIPAK antagonism.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32292165.
- Also identified by DOI 10.7554/eLife.54863 and PMC identifier 7182433.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The MST-LATS kinase cascade is central to the Hippo pathway that controls tissue homeostasis, development, and organ size. The PP2A complex STRIPAK<sup>SLMAP</sup> 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 STRIPAK<sup>SLMAP</sup>. 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.
Medical subject headings
- Cell Cycle Proteins
- Intracellular Signaling Peptides and Proteins
- Protein Phosphatase 2
- Protein Serine-Threonine Kinases