Smad2, Smad3 and Smad4 proteins are considered to be key mediators of transforming growth factor-beta (TGF-beta) signaling. However, the identities of the Smad partners mediating TGF-beta signaling are not fully understood. Here, we show that RNA-binding protein with multiple splicing (RBPMS), a member of the RNA-binding protein family, physically interacts with Smad2, Smad3 and Smad4 both in v...

Upon stimulation of cells with transforming growth factor β (TGF-β), Smad proteins form trimeric complexes and activate a broad spectrum of target genes. It remains unresolved which of the possible Smad complexes are formed in cellular contexts and how these contribute to gene expression. By combining quantitative mass spectrometry with a computational selection strategy, we predict and provide...

Despite advances in radiation delivery protocols, exposure of normal tissues during the course of radiation therapy remains a limiting factor of cancer treatment. If the canonical TGF-β/Smad pathway has been extensively studied and implicated in the development of radiation damage in various organs, the precise modalities of its activation following radiation exposure remain elusive. In the pre...

Smad proteins are critical intracellular mediators of the transforming growth factor-beta, bone morphogenic proteins (BMPs), and activin signaling. Upon ligand binding, the receptor-associated R-Smads are phosphorylated by the active type I receptor serine/threonine kinases. The phosphorylated R-Smads then form heteromeric complexes with Smad4, translocate into the nucleus, and interact with va...

TGF-beta and BMP receptor kinases activate Smad transcription factors by C-terminal phosphorylation. We have identified a subsequent agonist-induced phosphorylation that plays a central dual role in Smad transcriptional activation and turnover. As receptor-activated Smads form transcriptional complexes, they are phosphorylated at an interdomain linker region by CDK8 and CDK9, which are componen...

Runx factors control lineage commitment and are transcriptional effectors of Smad signaling. Genetic defects in these pathways interfere with normal development. The in situ localization of Runx and Smad proteins must impact the mechanisms by which these proteins function together in gene regulation. We show that the integration of Runx and Smad signals is mediated by in situ interactions at sp...

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...

We report that exposure of mouse embryonic fibroblasts to transforming growth factor beta-1 (TGFbeta-1) (5 ng/ml) results in a strong activation of p8 mRNA expression that precedes the induction of cell growth. Involvement of the p8 promoter in the regulation was demonstrated by using a p8-chloramphenicol acetyltransferase construct. We therefore speculated that p8 might be a mediator of TGFbet...

Transforming growth factor beta (TGF-beta) signaling via Smad proteins occurs in various cell types. However, whereas the biological response to TGF-beta can be as distinct as growth promoting (i.e., mesenchymal cells) versus growth inhibiting (i.e., epithelial cells), few discernible differences in TGF-beta signaling have been reported. In the current study, we examined the role of Ras in the ...