Phosphorylation of activation functions AF-1 and AF-2 of RAR alpha and RAR gamma is indispensable for differentiation of F9 cells upon retinoic acid and cAMP treatment

被引：93

作者：

Taneja, R ^{[1
]}

RochetteEgly, C ^{[1
]}

Plassat, JL ^{[1
]}

Penna, L ^{[1
]}

Gaub, MP ^{[1
]}

Chambon, P ^{[1
]}

机构：

[1] COLL FRANCE, INST GENET & BIOL MOL & CELLULAIRE,CNRS,INSERM,ULP, F-67404 ILLKIRCH GRAFFENSTADEN, FRANCE

来源：

EMBO JOURNAL | 1997年 / 16卷 / 21期

关键词：

parietal endoderm; primitive endoderm; proline-directed kinases; protein kinase A; signal transduction;

D O I：

10.1093/emboj/16.21.6452

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The role of RAR alpha 1 and RAR gamma 2 AF-1 and AF-2 activation functions and of their phosphorylation was investigated during RA-induced primitive and parietal differentiation of F9 cells. We found that: (i) primitive endodermal differentiation requires RAR gamma 2, whereas parietal endodermal differentiation requires both RAR gamma 2 and RAR alpha 1, and in all cases AF-1 and AF-2 must synergize; (ii) primitive endodermal differentiation requires the proline-directed kinase site of RAR gamma 2-AF-1, whereas parietal endodermal differentiation additionally requires that of RAR alpha 1-AF-1; (iii) the cAMP-induced parietal endodermal differentiation also requires the protein kinase A site of RAR alpha-AF-2, but not that of RAR gamma; and (iv) the AF-1-AF-2 synergism and AF-1 phosphorylation site requirements for RA-responsive gene induction are promoter context-dependent. Thus, AF-1 and AF-2 of distinct RARs exert specific cellular and molecular functions in a cell-autonomous system mimicking physiological situations, and their phosphorylation by kinases belonging to two main signalling pathways is required to enable RARs to transduce the RA signal during F9 cell differentiation.

引用

页码：6452 / 6465

页数：14

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