Editors' ChoiceImmunology

TGF-β Specificity in Immune Cells

Science's STKE  15 Jan 2002:
Vol. 2002, Issue 115, pp. tw29
DOI: 10.1126/stke.2002.115.tw29

Although there are about 30 known members of the transforming growth factor-β (TGF-β) superfamily, only two known cognate receptors have been characterized thus far, and only a few intracellular signal transducing molecules called Smads are known to mediate their effects in the nucleus. Few Smads bind to DNA directly to regulate gene expression, and other Smads bind to transcriptional cofactors that are ubiquitously expressed. Therefore, the wide range and tissue-specific effects of TGF-β-like factors are not well understood. Blokzijl et al. report that, in immune cells, TGF-β induces the Smad3 assocation with GATA-3, a transcription factor whose family has been implicated in regulating cell-fate decisions in the immune and nervous systems. Expression of Smad3 in a T cell line increased GATA-3-mediated activation of a reporter gene in response to TGF-β treatment. GATA-3 specifically associated with Smad3 and not with other Smad proteins when overexpressed in cells, and sites of interaction between the two proteins were identified. TGF-β also stimulated Smad3-GATA-3 complex formation in the nucleus of a T cell line. Overexpression of dominant negative forms of either Smad3 or GATA-3 in a T cell line inhibited cytokine production. Hence, GATA-3 is a tissue-specific partner of Smad3 and may underlie cell type-specific genes expression and T cell development induced by TGF-β.

A. Bloksijl, P. ten Dijke, C. F. Ibanez, Physical and functional interaction between GATA-3 and Smad3 allows TGF-β regulation of target genes. Current Biol. 12, 35-45 (2002). [Online Journal]