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

Yutaka Hashimoto, Noriyuki Kinoshita, Todd M. Greco, Joel D. Federspiel, Pierre M. Jean Beltran, Naoto Ueno, Ileana M. Cristea

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)226-241.e7
JournalCell Systems
Volume8
Issue number3
DOIs
StatePublished - Mar 27 2019

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

Keywords

  • Xenopus laevis
  • mass spectrometry
  • mechanical signaling
  • mechanobiology
  • mechanosensing
  • phosphoproteomics
  • phosphorylation
  • proteomics
  • signaling

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