Retinoic acid stimulates protein kinase A-associated G proteins during human teratocarcinoma differentiation Journal Article


Authors: Kurie, J. M.; Allopenna, J.; Dmitrovsky, E.
Article Title: Retinoic acid stimulates protein kinase A-associated G proteins during human teratocarcinoma differentiation
Abstract: Retinoic acid (RA) treatment of F9 murine teratocarcinoma (TC) cells reduces the expression of the protein kinase A (PKA)-associated G protein, G(alpha i2). The present study reveals interactions between the RA and PKA pathways during differentiation of the multipotent human TC cell line NTERA-2 clone D1 (abbreviated NT2/D1) which differ from prior reports in F9 TC cells. Compared to untreated NT2/D1 cells, differentiated NT2/D1 cells expressed increased levels of G(alpha S) and G(alpha il,2) proteins as shown by both immunoblot analysis and cholera toxin- and pertussis toxin-induced ADP ribosylation. To further explore cooperation between these pathways during human TC differentiation, we examined the effects of cyclic adenosine monophosphate (cAMP) on RA-responsive genes and of RA treatment on the transcriptional activation of a cAMP response element (CRE). Compared to RA alone, combined treatment with RA and cAMP augmented the expression of the RA nuclear receptor-beta (RAR-beta). Also, transient transfection assays revealed that cAMP and RA cooperated to enhance CRE transcriptional activation. The cAMP-induced enhancement of RA actions in NT2/D1 cells extended to immunophenotypic changes typical of the neuronal differentiation program induced by RA. In contrast to these findings in NT2/D1 cells, prior work in F9 TC cells showed that cAMP inhibits the RA-mediated augmentation of RAR-beta expression and switches the differentiation program from visceral to parietal endoderm. Thus, unlike murine TC cells, in human NT2/D1 cells RA stimulates PKA-associated G proteins and PKA pathway activation enhances RA-mediated TC differentiation.
Keywords: dna; transcription; cyclic amp; protein kinase a; nuclear receptors; retinoic acid; g protein; expression; embryonal carcinoma-cells; line; thyroid-hormone; ribonucleic-acid; x-receptor; rxr-beta; retinoic acid nuclear receptor; teratocarcinoma differentiation; (human)
Journal Title: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Volume: 1222
Issue: 1
ISSN: 0167-4889
Publisher: Elsevier B.V.  
Date Published: 1994-05-26
Start Page: 88
End Page: 94
Language: English
ACCESSION: WOS:A1994NP34000011
DOI: 10.1016/0167-4889(94)90028-0
PROVIDER: wos
PUBMED: 8186270
Notes: Article -- Source: Wos
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  1. Jonathan M. Kurie
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