MAP4K Interactome Reveals STRN4 as a Key STRIPAK Complex Component in Hippo Pathway Regulation
- Cell Rep. 2020 Jul 7;32(1):107860. doi: 10.1016/j.celrep.2020.107860.
- 1. Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA.
- 2. School of Life Sciences, Westlake University, Hangzhou, Zhejiang Province 310024, China. Electronic address: [email protected].
- 3. Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: [email protected].
Mitogen-activated protein kinase kinase kinase kinases (MAP4Ks) constitute a mammalian STE20-like serine/threonine kinase subfamily. Recent studies provide substantial evidence for MAP4K family kinases in the Hippo pathway regulation, suggesting a broad role of MAP4Ks in human physiology and diseases. However, a comprehensive analysis of the regulators and effectors for this key kinase family has not been fully achieved. Using a proteomic approach, we define the protein-protein interaction network for human MAP4K family kinases and reveal diverse cellular signaling events involving this important kinase family. Through it, we identify a STRIPAK complex component, STRN4, as a generic binding partner for MAP4Ks and a key regulator of the Hippo pathway in endometrial Cancer development. Taken together, the results of our study not only generate a rich resource for further characterizing human MAP4K family kinases in numerous biological processes but also dissect the STRIPAK-mediated regulation of MAP4Ks in the Hippo pathway.