Cloning of a novel signaling molecule, AMSH-2, that potentiates transforming growth factor β signaling

BMC Cell Biology

Matthias Mann³  Akhilesh Pandey⁵  Aristidis Moustakas²  William P Schiemann⁴  Daisuke Nakajima¹  Irina Kratchmarova³  Nieves Ibarrola⁵ 

[1] Department of Genome Informatics, Kazusa DNA Research Institute, Chiba 292-0812, Japan;Ludwig Institute for Cancer Research, Uppsala, SE-751 24, Sweden;Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, DK-5230, Denmark;Department of Pediatrics, National Jewish Medical and Research Center, Goodman Building, K1011, Denver, CO 80206, U.S.A;McKusick-Nathans Institute of Genetic Medicine and Department of Biological Chemistry, Johns Hopkins University, Baltimore, MD 21205, U.S.A

关键词: phosphorylation;    serine/threonine kinase;    bioinformatics;    Signal transduction;   

Others  :  1088920
DOI  :  10.1186/1471-2121-5-2

 received in 2003-11-10, accepted in 2004-01-19,  发布年份 2004

【 摘 要 】

Background

Transforming growth factor-βs (TGF-βs), bone morphogenetic proteins (BMPs) and activins are important regulators of developmental cell growth and differentiation. Signaling by these factors is mediated chiefly by the Smad family of latent transcription factors.

Results

There are a large number of uncharacterized cDNA clones that code for novel proteins with homology to known signaling molecules. We have identified a novel molecule from the HUGE database that is related to a previously known molecule, AMSH (

a

ssociated

m

olecule with the

SH

3 domain of STAM), an adapter shown to be involved in BMP signaling. Both of these molecules contain a coiled-coil domain located within the amino-terminus region and a JAB (Domain in

J

un kinase

a

ctivation domain

b

inding protein and proteasomal subunits) domain at the carboxy-terminus. We show that this novel molecule, which we have designated AMSH-2, is widely expressed and its overexpression potentiates activation of TGF-β-dependent promoters. Coimmunoprecipitation studies indicated that Smad7 and Smad2, but not Smad3 or 4, interact with AMSH-2. We show that overexpression of AMSH-2 decreases the inhibitory effect of Smad7 on TGF-β signaling. Finally, we demonstrate that knocking down AMSH-2 expression by RNA interference decreases the activation of 3TP-lux reporter in response to TGF-β.

Conclusions

This report implicates AMSH and AMSH-2 as a novel family of molecules that positively regulate the TGF-β signaling pathway. Our results suggest that this effect could be partially explained by AMSH-2 mediated decrease of the action of Smad7 on TGF-β signaling pathway.

【 授权许可】

   
2004 Ibarrola et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

【 图 表 】

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