Mechanical Force Induces Phosphorylation-Mediated Signaling that Underlies Tissue Response and Robustness in Xenopus Embryos. Author Yutaka Hashimoto, Noriyuki Kinoshita, Todd Greco, Joel Federspiel, Pierre Beltran, Naoto Ueno, Ileana Cristea Publication Year 2019 Type Journal Article 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. Keywords Animals, Signal Transduction, Phosphorylation, Protein Processing, Post-Translational, Proteome, Xenopus laevis, Embryo, Nonmammalian, Mechanical Phenomena, Protein Kinase C, Centrifugation, Focal Adhesion Protein-Tyrosine Kinases Journal Cell Syst Volume 8 Issue 3 Pages 226-241.e7 Date Published 2019 Mar 27 ISSN Number 2405-4720 DOI 10.1016/j.cels.2019.01.006 Alternate Journal Cell Syst PMCID PMC6453581 PMID 30852251 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML