Vascular MAD s: Two novel MAD -related genes selectively inducible by flow in human vascular endothelium

Abstract

Vascular endothelium is an important transducer and integrator of both humoral and biomechanical stimuli within the cardiovascular system. Utilizing a differential display approach, we have identified two genes, Smad6 and Smad7,

Expression and regulation of intracellular SMAD signaling in scleroderma skin fibroblasts

“…While SMAD2 and SMAD3 work synergistically and in tandem with SMAD4 in transducing TGF␤ signals, the antagonistic SMAD7 binds to the TGF␤ receptor complex and prevents SMAD2/3 access, thereby blocking SMAD phosphorylation. Because its expression is rapidly induced by TGF␤ (22)(23)(24), SMAD7 serves a critical negative feedback function by limiting the amplitude and duration of cellular responses to TGF␤. In addition to inhibitory SMAD7, multiple other intracellular mechanisms to modulate the intensity of SMAD signaling have been characterized (25)(26)(27)(28).…”

A short amino-acid sequence in MH1 domain is responsible for functional differences between Smad2 and Smad3

“…Smad4 is the unique member of the second class of Smad proteins: central ones. The third class includes Smad6 and Smad7 which have been identi®ed as inhibitors of TGFb signalling (Imamura et al, 1997;Hayashi et al, 1997;Nakao et al, 1997;Topper et al, 1997;Hata et al, 1998a). Interestingly, Smad2 and Smad4 genes are tumor suppressor gene candidates found either deleted or mutated in a number of human cancers including pancreatic and colon carcinomas, providing compelling support for a role of TGFb signalling in the development of some cancers (Hahn et al, 1996;Eppert et al, 1996;Hata et al, 1997Hata et al, , 1998bShi et al, 1997).…”

Induction of apoptosis by Smad3 and down-regulation of Smad3 expression in response to TGF-β in human normal lung epithelial cells

“…Signaling mediators downstream of the receptors for the TGFb superfamily were recently identi®ed in a variety of organisms, and termed`Smad' in vertebrates . While seven Smad genes have been reported in the literature thus far, they can be classi®ed into three types according to their functions, i.e., receptor-activated Smads (Smad1 and Smad5 for BMP; Smad2 and Smad3 for TGF-b and activin), co-Smad (Smad4) and anti-Smads (Smad6 and Smad7) Derynck et al, 1996;Eppert et al, 1996;Gra et al, 1996;Hahn et al, 1996;Hayashi et al, 1997;Hoodless et al, 1996;Lechleider et al, 1996;Liu et al, 1996;Riggins et al, 1996;Thomsen, 1996;Topper et al, 1997;Yingling et al, 1996;Zhang et al, 1996). Smad2 and Smad3, the receptor-activated, TGFb signaling Smads, are known to be highly homologous with regard to amino acid sequence and structural characteristics, and both have been found to mediate TGF-b and activin signals by forming heteromers with Smad4 (Eppert et al, 1996;Gra et al, 1996;Riggins et al, 1996;Wrana and Pawson, 1997;Zhang et al, 1996).…”