Open AccessInteraction proteome of human H ippo signaling: modular control of the co‐activator YAP 1
Author(s) -
Hauri Simon,
Wepf Alexander,
Drogen Audrey,
Varjosalo Markku,
Tapon Nic,
Aebersold Ruedi,
Gstaiger Matthias
Publication year - 2013
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.1002/msb.201304750
Subject(s) - hippo signaling pathway , biology , microbiology and biotechnology , cell growth , signal transduction , cell , crosstalk , proteome , cell polarity , activator (genetics) , biochemistry , receptor , physics , optics
Tissue homeostasis is controlled by signaling systems that coordinate cell proliferation, cell growth and cell shape upon changes in the cellular environment. Deregulation of these processes is associated with human cancer and can occur at multiple levels of the underlying signaling systems. To gain an integrated view on signaling modules controlling tissue growth, we analyzed the interaction proteome of the human Hippo pathway, an established growth regulatory signaling system. The resulting high‐resolution network model of 480 protein‐protein interactions among 270 network components suggests participation of Hippo pathway components in three distinct modules that all converge on the transcriptional co‐activator YAP 1. One of the modules corresponds to the canonical Hippo kinase cassette whereas the other two both contain Hippo components in complexes with cell polarity proteins. Quantitative proteomic data suggests that complex formation with cell polarity proteins is dynamic and depends on the integrity of cell‐cell contacts. Collectively, our systematic analysis greatly enhances our insights into the biochemical landscape underlying human Hippo signaling and emphasizes multifaceted roles of cell polarity complexes in Hippo‐mediated tissue growth control.