SPARC regulates extracellular matrix organization through its modulation of integrin-linked kinase activity

Thomas H. Barker, Gretchen Baneyx, Marina Cardó-Vila, Gail A. Workman, Matt Weaver, Priya M. Menon, Shoukat Dedhar, Sandra A. Rempel, Wadih Arap, Renata Pasqualini, Viola Vogel, E. Helene Sage

Research output: Contribution to journalArticlepeer-review

155 Scopus citations

Abstract

SPARC, a 32-kDa matricellular glycoprotein, mediates interactions between cells and their extracellular matrix, and targeted deletion of Sparc results in compromised extracellular matrix in mice. Fibronectin matrix provides provisional tissue scaffolding during development and wound healing and is essential for the stabilization of mature extracellular matrix. Herein, we report that SPARC expression does not significantly affect fibronectin-induced cell spreading but enhances fibronectin-induced stress fiber formation and cell-mediated partial unfolding of fibronectin molecules, an essential process in fibronectin matrix assembly. By phage display, we identify integrin-linked kinase as a potential binding partner of SPARC and verify the interaction by co-mmunoprecipitation and colocalization in vitro. Cells lacking SPARC exhibit diminished fibronectin-induced integrin-linked kinase activation and integrin-linked kinase-dependent cell-contractile signaling. Furthermore, induced expression of SPARC in SPARC-null fibroblasts restores fibronectin-induced integrin-linked kinase activation, downstream signaling, and fibronectin unfolding. These data further confirm the function of SPARC in extracellular matrix organization and identify a novel mechanism by which SPARC regulates extracellular matrix assembly.

Original languageEnglish (US)
Pages (from-to)36483-36493
Number of pages11
JournalJournal of Biological Chemistry
Volume280
Issue number43
DOIs
StatePublished - Oct 28 2005
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'SPARC regulates extracellular matrix organization through its modulation of integrin-linked kinase activity'. Together they form a unique fingerprint.

Cite this