Phosphorylated fibronectin enhances cell attachment and upregulates mechanical cell functions
journal contributionposted on 23.08.2021, 12:38 by Garif Yalak, Jau-Ye Shiu, Ingmar SchoenIngmar Schoen, Maria Mitsi, Viola Vogel
A large number of extracellular matrix proteins have been found in phosphorylated states, yet little is known about how the phosphorylation of extracellular matrix proteins might affect cell functions. We thus tested the hypothesis whether the phosphorylation of fibronectin, a major adhesion protein, affects cell behavior. Controlled in vitro phosphorylation of fibronectin by a casein kinase II (CKII) significantly upregulated cell traction forces and total strain energy generated by fibroblasts on nanopillar arrays, and consequently other elementary cell functions including cell spreading and metabolic activity. Mass spectrometry of plasma fibronectin from healthy human donors then identified a constitutively phosphorylated site in the C-terminus, and numerous other residues that became phosphorylated by the CKII kinase in vitro. Our findings open up novel strategies for translational applications including targeting diseased ECM, or to develop assays that probe the phosphorylation state of the ECM or blood as potential cancer markers.
ERC Advanced Grant (European Research Council, Contract Nr. 233157)
Swiss Initiative in Systems Biology (SystemsX.ch, “Phosphorylation Modulated Networks of the Cell” (PhosphoNetX)
Swiss National Science Foundation (SNF, Contract Nr. 3100A0-116236)
CommentsThe original article is available at https://journals.plos.org
Published CitationYalak G, Shiu JY, Schoen I, Mitsi M, Vogel V. Phosphorylated fibronectin enhances cell attachment and upregulates mechanical cell functions. PLoS One. 2019;14(7):e0218893.
Publication Date10 July 2019
- School of Pharmacy and Biomolecular Sciences
- Irish Centre for Vascular Biology
- Biomaterials and Regenerative Medicine
- Vascular Biology
PublisherPublic Library of Science (PLoS)
- Published Version (Version of Record)
Cell LineFibroblastsAnimalsMiceCasein Kinase IIFibronectinsIntegrin alphaVbeta3Sequence AlignmentCell AdhesionMechanotransduction, CellularGene ExpressionBinding SitesAmino Acid SequenceProtein BindingSequence Homology, Amino AcidPhosphorylationKineticsThermodynamicsModels, MolecularProtein Interaction Domains and MotifsProtein Conformation, alpha-HelicalProtein Conformation, beta-StrandGeneral Science & Technology