A novel modulatory mechanism of transforming growth factor-ss signaling through decorin and LRP-1

Cabello-Verrugio, C; Brandan, E.

Abstract

Transforming growth factor-β (TGF-β) is a multifunctional cytokine that signals to the nucleus through cell surface transmembrane receptors with serine/threonine kinase activity and cytoplasmic effectors, including Smad proteins. Here we describe two novel modulators of this pathway, lipoprotein-receptor related protein (LRP-1) and decorin. Decorin null (Dcn null) myoblasts showed a diminished TGF-β response that is restored by decorin re-expression. Importantly, this reactivation occurs without changes in the binding to TGF-β receptors, Smad protein phosphorylation, or Smad-4 nuclear translocation. In wild type myoblasts, inhibition of decorin binding to LRP-1 and depletion of LRP-1 inhibited TGF-β response to levels similar to those observed in Dcn null myoblasts. Re-expression of decorin in Dcn null myoblasts cannot restore TGF-β response if the Smad pathway or phosphatidylinositol 3-kinase activity is inhibited, suggesting that this LRP-1-decorin modulatory pathway requires activation of the Smad pathway by TGF-β and involves phosphatidylinositol 3-kinase activity. This work unveils a new regulatory mechanism for TGF-β signaling by decorin and LRP-1. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.

Más información

Título según WOS: A novel modulatory mechanism of transforming growth factor-ss signaling through decorin and LRP-1
Título según SCOPUS: A novel modulatory mechanism of transforming growth factor-ß signaling through decorin and LRP-1
Título de la Revista: JOURNAL OF BIOLOGICAL CHEMISTRY
Volumen: 282
Número: 26
Editorial: Elsevier
Fecha de publicación: 2007
Página de inicio: 18842
Página final: 18850
Idioma: English
URL: http://www.jbc.org/cgi/doi/10.1074/jbc.M700243200
DOI:

10.1074/jbc.M700243200

Notas: ISI, SCOPUS