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Mol Cell Biol September 1, 2007; 27 (17): 6183-94.
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Erbin inhibits transforming growth factor beta signaling through a novel Smad-interacting domain.

Dai F , Chang C , Lin X , Dai P , Mei L , Feng XH .

Smad proteins are critical intracellular signaling mediators for the transforming growth factor beta (TGFbeta) superfamily. Here, we report that Erbin (for "ErbB2/Her2-interacting protein"), which contains leucine-rich repeats and a PDZ (PSD-95/DLG/ZO-1) domain, interacts specifically with Smad3 and, to a lesser extent, with Smad2 through a novel Smad-interacting domain (SID) adjacent to its PDZ domain. Increased expression of Erbin does not affect the level of TGFbeta-induced phosphorylation of Smad2/Smad3, but it physically sequesters Smad2/Smad3 from their association with Smad4 and hence negatively modulates TGFbeta-dependent transcriptional responses and cell growth inhibition. An isoform of Erbin encoded by an alternatively spliced transcript in human tissues lacks this SID and fails to inhibit TGFbeta responses. Consistently, knockdown of the endogenous Erbin gene with short hairpin RNA enhances TGFbeta-induced antiproliferative and transcriptional responses. In addition, Erbin suppresses activin/Smad2-dependent, but not BMP/Smad1-mediated, induction of endogenous gene expression in Xenopus embryos. Therefore, these results define Erbin as a novel negative modulator of Smad2/Smad3 functions and expand the physiological role of Erbin to the regulation of TGFbeta signaling.

PubMed ID: 17591701
PMC ID: PMC1952163
Article link: Mol Cell Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: dlg4 erbin psd smad1 smad2 smad3 smad4 smad4.2 tgfb1 tjp1
GO keywords: transforming growth factor beta receptor signaling pathway [+]

References [+] :
Apperson, Characterization of densin-180, a new brain-specific synaptic protein of the O-sialoglycoprotein family. 1996, Pubmed