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XB-ART-39594
J Biol Chem June 19, 2009; 284 (25): 17052-60.

Identification of a novel negative regulator of activin/nodal signaling in mesendodermal formation of Xenopus embryos.

Cheong SM , Kim H , Han JK .


Abstract
Phosphotyrosine binding (PTB) domains, which are found in a large number of proteins, have been implicated in signal transduction mediated by growth factor receptors. However, the in vivo roles of these PTB-containing proteins remain to be investigated. Here, we show that Xdpcp (Xenopus dok-PTB containing protein) has a pivotal role in regulating mesendoderm formation in Xenopus, and negatively regulates the activin/nodal signaling pathway. We isolated cDNA for xdpcp and examined its potential role in Xenopus embryogenesis. We found that Xdpcp is strongly expressed in the animal hemisphere at the cleavage and blastula stages. The overexpression of xdpcp RNA affects activin/nodal signaling, which causes defects in mesendoderm formation. In addition, loss of Xdpcp function by injection of morpholino oligonucleotides leads to the expansion of the mesodermal territory. Moreover, we found that axis duplication by ventrally forced expression of activin is recovered by coexpression with Xdpcp. In addition, Xdpcp inhibits the phosphorylation and nuclear translocation of Smad2. Furthermore, we also found that Xdpcp interacts with Alk4, a type I activin receptor, and inhibits activin/nodal signaling by disturbing the interaction between Smad2 and Alk4. Taken together, these results indicate that Xdpcp regulates activin/nodal signaling that is essential for mesendoderm specification.

PubMed ID: 19389709
PMC ID: PMC2719343
Article link: J Biol Chem

Genes referenced: a2m actl6a acvr1b bmp4 bmpr1a chrd.1 dok1 gsc mix1 msx1 myc nodal nodal1 odc1 ptbp1 smad1 smad2 sox17b.1 tbxt tgfb1 vegt ventx1.1
GO keywords: axis specification [+]
Antibodies: Smad1 Ab7 Smad2 Ab4
Morpholinos: dok1 MO1


Article Images: [+] show captions
References:
Bell, 2003, Pubmed, Xenbase [+]


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