RT Journal Article
SR Electronic
T1 Smad7 is required for TGF-β-induced activation of the small GTPase Cdc42
JF Journal of Cell Science
JO J. Cell Sci.
FD The Company of Biologists Ltd
SP 1835
OP 1847
DO 10.1242/jcs.01036
VO 117
IS 9
A1 Edlund, Sofia
A1 Landström, Maréne
A1 Heldin, Carl-Henrik
A1 Aspenström, Pontus
YR 2004
UL http://jcs.biologists.org/content/117/9/1835.abstract
AB Transforming growth factor β (TGF-β) is a potent regulator of cell growth and differentiation in many cell types. The Smad signaling pathway constitutes a main signal transduction route downstream of TGF-β receptors. The inhibitory Smads, Smad6 and Smad7, are considered to function as negative regulators of the TGF-β/Smad signaling cascade. In a previous study, we found that TGF-β induces rearrangements of the actin filament system in human prostate carcinoma cells and that this response requires the small GTPases Cdc42 and RhoA. On the basis of the current view on the function of Smad7 in TGF-β signaling, we hypothesized that Smad7 would function as a negative regulator of the TGF-β-induced activation of Cdc42 and RhoA, but instead we found that the reverse is the case; Smad7 is required for the TGF-β-induced activation of Cdc42 and the concomitant reorganization of the actin filament system. These observations propose a novel role for Smad7 in TGF-β-dependent activation of Rho GTPases.