RGD Reference Report - Involvement of Smad proteins in the differentiation of pancreatic AR42J cells induced by activin A. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Involvement of Smad proteins in the differentiation of pancreatic AR42J cells induced by activin A.

Authors: Zhang, YQ  Kanzaki, M  Furukawa, M  Shibata, H  Ozeki, M  Kojima, I 
Citation: Zhang YQ, etal., Diabetologia 1999 Jun;42(6):719-27.
RGD ID: 69876
Pubmed: PMID:10382592   (View Abstract at PubMed)
DOI: DOI:10.1007/s001250051220   (Journal Full-text)

AIMS/HYPOTHESIS: Activin A induces differentiation of amylase-secreting pancreatic AR42J cells into endocrine cells. This study assesses the role of Smad proteins in the actions of activin A in AR42J cells. METHODS: The expression of Smad proteins was determined by northern blotting. Phosphorylation and translocation of Smad2 was measured by transfecting flag-tagged Smad2. Involvement of Smad2 was examined by transfecting cDNA encoding N-terminal and C-terminal domains of Smad2. RESULTS: The mRNAs for Smad2 and Smad4 were abundantly expressed whereas the expression of mRNA for Smad1 and Smad3 was very low. Activin A induced serine-phosphorylation and the subsequent accumulation of the Smad2 in nuclei. Transfection of the N-terminal domain of Smad2, which acts as a dominantly negative mutant (Smad2-N), blocked the morphological changes induced by activin A whereas the C-terminal domain of Smad2, which acts as a constitutively active mutant (Smad2-C), reproduced the activin-induced morphological changes. Similarly, Smad2-N blocked apoptosis induced by activin A and Smad2-C induced apoptosis. Activin A converted AR42J into insulin-secreting cells in the presence of hepatocyte growth factor and introduction of Smad2-N inhibited the differentiation. Smad2-C, however, did not induce differentiation in the presence of hepatocyte growth factor. CONCLUSIONS/INTERPRETATION: Activation of the Smad2 pathway is necessary and sufficient to induce apoptosis and morphological changes. Although activation of the Smad2 pathway is required, it is not solely sufficient for the differentiation of AR42J into endocrine cells.

Objects referenced in this article
Gene Smad2 SMAD family member 2 Rattus norvegicus

Additional Information