Extracellular matrix-induced transforming growth factor-Β receptor signaling dynamics

N. Garamszegi, S. P. Garamszegi, P. Samavarchi-Tehrani, E. Walford, Michaela Schneiderbauer, J. L. Wrana, S. P. Scully

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Matrix remodeling, degradation, inflammation and invasion liberate peptide fragments that can subsequently interact with cells in an attachment-independent manner. Such soluble matrix components, including collagens, fibronectin and laminin, induced Smad activation (termed crosstalk signaling), which follows a similar chronological sequence and R-Smad specificity as induced by transforming growth factor (TGF)-Β1. Smad4 nuclear translocation occurred in response to collagen binding, indicating downstream signal propagation. TGF-Β scavenging antibody affected only TGF-Β1, but not crosstalk-induced responses. TGF-Β type II receptor mutation (DR26Δ25), which is deficient in TGF-Β type I receptor recruitment to the ligand, induced a heterotetramer signaling complex, and propagated Smad2 activation only through collagen induction and not TGF-Β signaling. Consequentially, TGF-Β ligand participation is not required for crosstalk signaling. This signaling requires a functional integrin Β1 receptor as showed by RNA interference. Co-immunoprecipitation (co-IP) and fluorescent microscopy indicate the involvement of focal adhesion kinase (FAK) and Src activity in collagen-induced signal propagation, and suggest a membrane signaling complex formation that includes both TGF-Β receptors and integrins. The related gene expressional responses are distinct from that evoked by TGF-Β1, supporting its separate function. This signaling mechanism expands and partially explains TGF-Β receptor dynamics and consequential signaling diversity-related gene expressional plasticity.

Original languageEnglish
Pages (from-to)2368-2380
Number of pages13
JournalOncogene
Volume29
Issue number16
DOIs
StatePublished - Apr 1 2010

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Keywords

  • Attachment-independent signaling
  • Extracellular matrix
  • Gene expressional plasticity
  • Smads
  • TGF-β and integrin receptors

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Garamszegi, N., Garamszegi, S. P., Samavarchi-Tehrani, P., Walford, E., Schneiderbauer, M., Wrana, J. L., & Scully, S. P. (2010). Extracellular matrix-induced transforming growth factor-Β receptor signaling dynamics. Oncogene, 29(16), 2368-2380. https://doi.org/10.1038/onc.2009.514