Smad signaling pathway

Figure 2 SMAD signaling pathway, in which ligand binding activates the dimer formation of type I and type II receptors, which initiate intracellular signaling.

Table 6.2 Consequences of mutations of genes encoding components of the TGE p/SMAD signalling pathway (reproduced with permission of the author and Annu Rev. Biochem. from Rg. 7 in ref. 1)...

The TG F/ /Smad signaling pathway is controlled at various levels and is subjected to crosstalk with other signaling pathways (Fig. 12.2). The main regulatory influences are listed below (review Kloos et al., 2002). 

Liu, H., Peng, H., Wu, Y, et al., 2013. The promotion of bone regeneration by nanolibrous hydroxyapatite/chitosan scaffolds by effects on integrin-BMP/Smad signaling pathway in BMSCs. Biomaterials 32 (18), 4404-4417. 

In total, TGPP-Smad signal conduction has distinct similarities to signal conduction in the Jak-Stat pathway (see 11.1.3). In both pathways, cytosolic transcription factors are activated by phosphorylation and are translocated in oligomeric complexes to the nucleus and the DNA. Common to both pathways is the short distance from the extracellular signal to the transcription level. 

Ulloa, L., Doody, J. and Massague, J. Inhibition of transforming growth factor-beta/SMAD signalling by the interferon-gamma/STAT pathway (1999) Nature 397, 710-713... 

Lagna, G., Hata, A., Hemmati-Brivanlou, A., and Massague, J. 1996. Partnership between DPC4 and SMAD proteins in TGF-beta signalling pathways. Nature 383 832-836. 

Suzuki, H., Yagi, K., Kondo, M., Kato, M., Miyazono, K., and Miyazawa, K. 2004. c-Ski inhibits the TGF-beta signaling pathway through stabilization of inactive Smad complexes on Smad-binding elements. Oncogene 23 5068-5076. 

Both of these strategies have broader applications than the kinase signaling pathways. Orthogonal ligand-receptor pairs could, theoretically, be made for any ligand-receptor pair. These pairs could then be used to study metabolic pathways and protein function, to identify smaD-molecule ligands and other applications. 

Mehra, A. and Wrana, J.L. (2002) TGF-beta and the Smad signal transduction pathway. Biochem.Cell Biol., 80, 605-622. 

Researchers Identified the transcription factors downstream from TGFp receptors In Drosophila from genetic studies similar to those used to dissect receptor tyrosine kinase pathways (see Section 14.3). These transcription factors in Drosophila and the related vertebrate proteins are now called Smads. Three types of Smad proteins function in the TGFp signaling pathway receptor-regulated Smads (R-Smads), co-Smads, and Inhibitory or antagonistic Smads (TSmads). 

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