Identification of a novel negative regulator of activin/nodal signaling in mesendodermal formation of Xenopus embryos.
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.
Cheong
Seong-Moon
SM
From the Department of Life Sciences, Pohang University of Science and Technology, San 31, Hyoja Dong, Pohang, Kyungbuk 790-784, Republic of Korea.
Kim
Hyunjoon
H
From the Department of Life Sciences, Pohang University of Science and Technology, San 31, Hyoja Dong, Pohang, Kyungbuk 790-784, Republic of Korea.
Han
Jin-Kwan
JK
From the Department of Life Sciences, Pohang University of Science and Technology, San 31, Hyoja Dong, Pohang, Kyungbuk 790-784, Republic of Korea. Electronic address: jkh@postech.ac.kr.
D028341:Activins / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D004707:Endoderm / Q000196:embryology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D008954:Models, Biological; D055457:Nodal Protein / Q000378:metabolism*; D019000:Phosphotyrosine / Q000378:metabolism; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*
D017931:DNA Primers; D055457:Nodal Protein; D051899:Smad2 Protein; C497785:Smad2 protein, Xenopus; D029867:Xenopus Proteins; D028341:Activins; D019000:Phosphotyrosine