Smads are intracellular transducers for TGF-beta superfamily ligands, but little is known about the mechanism by which complexes of receptor-phosphorylated Smad2 and Smad4 regulate transcription. Using an in vitro transcription system, we have discovered that, unlike most transcription factors that are sufficient to recruit the basal transcription machinery and therefore activate transcription ...

Recent studies of the Smad family proteins, which are the key signal transducers of the TGF-beta family ligands, have revealed the ability of Smads to interact with various components of the 26S proteasome system. Such interactions are now known to contribute to the regulation of Smad protein levels before and after Smad activation. Most importantly, such interactions are also shown to be an in...

Smad proteins are signaling intermediates of the TGF-beta superfamily and are involved in a range of biological activities including development and immune responses. We studied the expression of TGF-beta-receptor activated Smads (Smad2 and Smad3), the common partner Smad (Smad4), an inhibitory Smad (Smad7), and the activated (phosphorylated) Smad2 (pSmad2) in developing and adult kidneys of hu...

Insulin resistance (IR) plays a major role in the pathogenesis of abdominal obesity, hypertension, coronary heart disease, atherosclerosis and diabetes. miR-21 and TGF-β/smads is closely related to IR. However, it remained elusive whether metformin improved skeletal muscle insulin resistance (IRSM) by regulating miR-21 and its target signal TGF-β1/smads expression. In this study, high-fat diet ...

TGF-beta inhibits adipocyte differentiation, yet is expressed by adipocytes. The function of TGF-beta in adipogenesis, and its mechanism of action, is unknown. To address the role of TGF-beta signaling in adipocyte differentiation, we characterized the expression of the TGF-beta receptors, and the Smads which transmit or inhibit TGF-beta signals, during adipogenesis in 3T3-F442A cells. We found...

Smad6 and Smad7 are inhibitory SMADs with putative functional roles at the intersection of major intracellular signaling networks, including TGF, receptor tyrosine kinase (RTK), JAK/STAT, and NFB pathways. This study reports differential functional roles and regulation of Smad6 and Smad7 in TGFsignaling in renal cells, in murine models of renal disease and in human glomerular diseases. Smad7 is...