Liu, Lan, Rachel Santora, Jaladanki N. Rao, Xin Guo, Tongtong Zou, Huifang M. Zhang, Douglas J. Turner, and Jian-Ying Wang. Activation of TGF-Smad signaling pathway following polyamine depletion in intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 285: G1056–G1067, 2003. First published July 10, 2003; 10.1152/ajpgi.00151.2003.—Smad proteins are transcription activators that a...

Signals from transforming growth factor-beta (TGF-beta) ligands are transmitted within the cell by members of the Smad family, which can be grouped into three classes based on sequence similarities. Our previous identification of both class I and II Smads functioning in a single pathway in C. elegans, raised the issue of whether the requirement for Smads derived from different classes is a gene...

Smad6 and Smad7 comprise a subclass of vertebrate Smads that antagonize, rather than transduce, TGF-beta family signaling. These Anti-Smads can block BMP signaling, as evidenced by their ability to induce a secondary dorsal axis when misexpressed ventrally in Xenopus embryos. Smad7 inhibits additional TGF-beta related pathways, and causes spina bifida when misexpressed dorsally. We have perform...

binding by the ternary Smad–FAST complex. Smad3 can bers are a group of secreted polypeptides that regulate replace Smad2 in this complex and at the Mix.2 element a diverse array of developmental and biological pro-can activate transcription (Yeo et al., 1999), whereas at the cesses. Disruption of the ligands or of components of goosecoid promoter Smad3 blocks activation (Labbé et their signali...

TGFbeta signaling controls diverse normal developmental processes and pathogenesis of diseases including cancer and autoimmune and fibrotic diseases. TGFbeta responses are generally mediated through transcriptional functions of Smads. A key step in TGFbeta signaling is ligand-induced phosphorylation of receptor-activated Smads (R-Smads) catalyzed by the TGFbeta type I receptor kinase. However, ...

Smad1, Smad5 and Smad9 (also known as Smad8) are activated by phosphorylation by bone morphogenetic protein (BMP)-bound type I receptor kinases. We examined the role of Smad1, Smad5, and Smad9 by creating constitutively active forms (Smad(DVD)). Transcriptional activity of Smad9(DVD) was lower than that of Smad1(DVD) or Smad5(DVD), even though all three Smad(DVD)s associated with Smad4 and boun...

Bone morphogenetic proteins (BMPs) control numerous processes in developing and adult organisms by binding to receptors on various cell types. The signals are relayed to the nucleus by signaling molecules called Smads. How the Smads are recruited to BMP receptors has been difficult to establish. In a paper appearing in this issue of Journal of Cell Science, Shi and colleagues show that a lipid-...

BACKGROUND Initiation, amplitude, duration and termination of transforming growth factor β (TGFβ) signaling via Smad proteins is regulated by post-translational modifications, including phosphorylation, ubiquitination and acetylation. We previously reported that ADP-ribosylation of Smads by poly(ADP-ribose) polymerase 1 (PARP-1) negatively influences Smad-mediated transcription. PARP-1 is known...