Trends Biochem Sci. 2004 May;29(5):265-73.

New insights into TGF-beta-Smad signalling.

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Division of Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.

Abstract

Transforming growth factor beta (TGF-beta) initiates its diverse cellular responses by binding to and activating specific cell surface receptors that have intrinsic serine/threonine kinase activity. These activated TGF-beta receptors stimulate the phosphorylation of receptor-regulated Smad proteins, which in turn form complexes with Smad4 that accumulate in the nucleus and regulate the transcription of target genes. TGF-beta responses can be cell-type specific and are dependent on both the concentration of TGF-beta signalling components and the activity of other signal transduction pathways, which can either synergize with or antagonize the TGF-beta pathway. Recent research has provided insights into the specificity determinants of TGF-beta-Smad signalling, including combinatorial ligand-receptor associations, selective interactions between the Smads and other pathway components that are mediated through defined binding motifs, and the differential regulation of duration and intensity of signalling.

PMID:: 15130563; [PubMed - indexed for MEDLINE]

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