TGFβ Assay (TGF-beta Assay) SMAD2/SMAD3/SMAD4

TGF-β Overview

TGF-β is a member of a family of dimeric polypeptide growth factors that includes bone morphogenic proteins and activins. All of these growth factors share a cluster of conserved cysteine residues that form a common cysteine knot structure held together by intramolecular disulfide bonds. Virtually every cell in the body, including epithelial, endothelial, hematopoietic, neuronal, and connective-tissue cells, produces TGF-β and has receptors for it. TGF-β regulates the proliferation and differentiation of cells, embryonic development, wound healing, and angiogenesis. The essential role of the TGF-β signaling pathway in these processes has been demonstrated by targeted deletion of the genes encoding members of this pathway in mice.

TGF-β and diseases

Increases or decreases in the production of TGF-β have been linked to numerous disease states, including atherosclerosis and fibrotic disease of the kidney, liver, and lung, and cancers. Mutations in the genes for TGF-β, its receptors, or intracellular signaling molecules associated with TGF-β are also important in the pathogenesis of disease, particularly cancer and hereditary hemorrhagic telangiectasia. Our SMAD Reporter assay is designed to monitor the activity of TGF-β -induced signal transduction pathways in cultured cells. The TGF-β signaling pathway is involved in many cellular processes, including cell cycle arrest, differentiation, homeostasis, and immunosuppression. TGF-β signaling induces phosphorylation and activation of the SMAD2 and SMAD3 proteins, which then form complexes with the mediator SMAD4. These SMAD complexes are then translocated to the nucleus, where they activate the expression of TGF-β-responsive genes. The TGF-β-responsive luciferase construct encodes the firefly luciferase reporter gene under the control of a promoter of the SMAD transcriptional response element (TRE).

Related References to TGF-β:

1. Cacheaux, L. P., Ivens, S., David, Y., Lakhter, A. J., Bar-Klein, G., Shapira, M., Heinemann, U., Friedman, A., and Kaufer, D. Transcriptome profiling reveals TGF-beta signaling involvement in epileptogenesis. J Neurosci, 29: 8927-8935, 2009.
2. Konigshoff, M., Kneidinger, N., and Eickelberg, O. TGF-beta signaling in COPD: deciphering genetic and cellular susceptibilities for future therapeutic regimen. Swiss Med Wkly, 139: 554-563, 2009.
3. Liu, Y., Wen, X. M., Lui, E. L., Friedman, S. L., Cui, W., Ho, N. P., Li, L., Ye, T., Fan, S. T., and Zhang, H. Therapeutic targeting of the PDGF and TGF-beta-signaling pathways in hepatic stellate cells by PTK787/ZK22258. Lab Invest, 89: 1152-1160, 2009.
4. McCaffrey, T. A. TGF-beta signaling in atherosclerosis and restenosis. Front Biosci (Schol Ed), 1: 236-245, 2009.
5. Roussa, E., von Bohlen und Halbach, O., and Krieglstein, K. TGF-beta in dopamine neuron development, maintenance and neuroprotection. Adv Exp Med Biol, 651: 81-90, 2009.
6. Tossidou, I., Starker, G., Kruger, J., Meier, M., Leitges, M., Haller, H., and Schiffer, M. PKC-alpha modulates TGF-beta signaling and impairs podocyte survival. Cell Physiol Biochem, 24: 627-634, 2009.
7. Yan, X., Liu, Z., and Chen, Y. Regulation of TGF-beta signaling by Smad7. Acta Biochim Biophys Sin (Shanghai), 41: 263-272, 2009.