TY - JOUR
T1 - Retinoic acid stimulates protein kinase A-associated G proteins during human teratocarcinoma differentiation
AU - Kurie, Jonathan M.
AU - Allopenna, Janet
AU - Dmitrovsky, Ethan
N1 - Funding Information:
This work was supported by No. DB-47C and DB-47B, a Special Grant for Research from the American Cancer Society, New York City Division. J.K. was supported by the Brian Piccollo Fund and by NIH Grant 1F32CA08940-03. We thank Dr. Wolfgang Maerz for his helpful consultation and assistance in the completion of the manuscript. We thank Ms. Tina Vazquez for her expert secretarial assistance.
PY - 1994/5/26
Y1 - 1994/5/26
N2 - Retinoic acid (RA) treatment of F9 murine teratocarcinoma (TC) cells reduces the expression of the protein kinase A (PKA)-associated G protein, Gαi2. 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 Gαs and Gαi1,2 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-β (RAR-β). 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-β 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.
AB - Retinoic acid (RA) treatment of F9 murine teratocarcinoma (TC) cells reduces the expression of the protein kinase A (PKA)-associated G protein, Gαi2. 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 Gαs and Gαi1,2 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-β (RAR-β). 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-β 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.
KW - (Human)
KW - G protein
KW - Protein kinase A
KW - Retinoic acid
KW - Retinoic acid nuclear receptor
KW - Teratocarcinoma differentiation
KW - cyclic AMP
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U2 - 10.1016/0167-4889(94)90028-0
DO - 10.1016/0167-4889(94)90028-0
M3 - Article
C2 - 8186270
AN - SCOPUS:0028332740
SN - 0167-4889
VL - 1222
SP - 88
EP - 94
JO - BBA - Molecular Cell Research
JF - BBA - Molecular Cell Research
IS - 1
ER -