Mechanical Force Induces Phosphorylation-Mediated Signaling that Underlies Tissue Response and Robustness in Xenopus Embryos.

TitleMechanical Force Induces Phosphorylation-Mediated Signaling that Underlies Tissue Response and Robustness in Xenopus Embryos.
Publication TypeJournal Article
Year of Publication2019
AuthorsHashimoto, Y, Kinoshita, N, Greco, TM, Federspiel, JD, Beltran, PMJean, Ueno, N, Cristea, IM
JournalCell Syst
Volume8
Issue3
Pagination226-241.e7
Date Published2019 Mar 27
ISSN2405-4720
Abstract

Mechanical forces are essential drivers of numerous biological processes, notably during development. Although it is well recognized that cells sense and adapt to mechanical forces, the signal transduction pathways that underlie mechanosensing have remained elusive. Here, we investigate the impact of mechanical centrifugation force on phosphorylation-mediated signaling in Xenopus embryos. By monitoring temporal phosphoproteome and proteome alterations in response to force, we discover and validate elevated phosphorylation on focal adhesion and tight junction components, leading to several mechanistic insights into mechanosensing and tissue restoration. First, we determine changes in kinase activity profiles during mechanoresponse, identifying the activation of basophilic kinases. Pathway interrogation using kinase inhibitor treatment uncovers a crosstalk between the focal adhesion kinase (FAK) and protein kinase C (PKC) in mechanoresponse. Second, we find LIM domain 7 protein (Lmo7) as upregulated upon centrifugation, contributing to mechanoresponse. Third, we discover that mechanical compression force induces a mesenchymal-to-epithelial transition (MET)-like phenotype.

DOI10.1016/j.cels.2019.01.006
Alternate JournalCell Syst
PubMed ID30852251
PubMed Central IDPMC6453581
Grant ListR01 HL135007 / HL / NHLBI NIH HHS / United States