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Session II : Receptor signaling and G proteins Poster II, 41
Endoglin modulates Transforming Growth Factor-beta signaling pathways in L6E9
myoblasts
Alicia Rodríguez-Barbero, Soraya Velasco, José M. López-Novoa
Instituto Reina Sofía de Investigación Nefrológica. Dpto de Fisiología y Farmacología.
Universidad de Salamanca. Campus Unamuno, Edificio Departamental. Avda. Campo
Charro s/n. 37007. Salamanca. Spain. E-mail: barberoa@usal.es
Endoglin is a transmembrane accessory receptor for transforming growth factor-# (TGF-#).
TGF-# elicits cellular responses via specific type I and II serine/threonine kinase receptors
and their downstream nuclear effectors, termed Smads. Type I receptors act downstream of
type II receptors and determine the signalling specificity within the receptor complex. In most
cells, TGF-# signals via TGF-# type II receptor and activin receptor-like kinase (ALK) 5 to
induce Smad2/3 phosphorylation. However, it has recently been shown that in endothelial
cells TGF-# activates two distinct types I receptor pathways, that is, ALK5-inducing Smad2/3
phosphorylation and ALK1-promoting Smad1/5 phosphorylation. Endoglin, as well as other
TGF-# signaling components, is involved in several pathophysiological processes such as
angiogenesis and fibrosis. Mutations in endoglin and ALK1 have been linked to the vascular
disorder, hereditary hemorrhagic telangiectasia type 1 (HHT1). However, the function of
endoglin in TGF-#/ALK signalling has remained unclear. To assess the function of endoglin
in TGF-#/ALK signalling, we select a non-endoglin expressed cell type such as L6E9 rat
myoblasts, and transfected them with L-endoglin. We found that both, the classic TGF-
#/ALK5 and the endothelial specific TGF-#/ALK1 pathways are present and functional in
L6E9 myoblasts. TGF-#1 activated both Smad1 y Smad2/3 and also induced Smad2/3 and
Smad4 nuclear translocation without differences between mock and endoglin transfected
myoblasts. Nevertheless, endoglin promote Id1 expression and reduce PAI-1 activity. Our
results indicate a pivotal role for endoglin in the balance of ALK1 and ALK5 signalling. The
progression in our understanding on the functional role of endoglin might have important
relevance in the regulation of pathophysiological processes in which endoglin is involved.
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