Cited by 124Retinoids in leukemia and cellular processesPeroxisome Proliferator-Activated ReceptorsProtein Kinase Regulation and GTPase Signaling

Phosphorylation of the retinoic acid receptor-alpha by protein kinase A

Open access
Rochette-Egly, C.·1995·Molecular Endocrinology

Abstract

The phosphorylation of retinoic acid receptor-alpha 1 (RAR alpha 1) by PKA was investigated both in vitro and in vivo. We show that bacterially expressed RAR alpha 1 is phosphorylated in vitro by protein kinase A (PKA) at the unique serine residue 369 located in the C-terminal end of the E region. We also show that RAR alpha 1 overexpressed in COS-1 cells is phosphorylated on multiple serine residues and that phosphorylation at serine 369 occurs only when COS-1 cells are cotransfected with PKA or treated with forskolin. RAR alpha 1 mutants were constructed in which serine 369 was replaced by an alanine (S369A) or a glutamic acid (S369E) residue. Comparison of the tryptic phosphopeptide patterns of wild type and mutated RAR alpha 1 overexpressed in COS-1 cells allowed us to confirm that serine 369 is the unique phosphorylation site for PKA in cultured cells. The DNA-binding efficiency of RAR alpha/retinoid X receptor-alpha (RXR alpha) heterodimers was enhanced in vitro by the S369E mutation. However, in transfected RAC65 cells, the same S369E mutation did not affect the ligand-dependent transcriptional activation by RAR alpha 1 of reporter genes containing a retinoic acid (RA)-response element. In contrast, the S369A mutation slightly decreased both DNA binding and the efficiency of PKA to enhance RA-induced transactivation by RAR alpha 1. Finally, we show that endogenous RAR alpha is also phosphorylated in vivo at serine 369 in forskolin-treated F9 cells, supporting the idea that phosphorylation of RARs at this site is involved in the modulation of the RA-induced differentiation of F9 cells by (Bu)2cAMP.

Integrity signals

Registry

Crossref · 10.1210/me.9.7.860

Cites

46 of 46 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • RARs are phosphorylated at two serine residues, one in the LBD (serine 369 in RARα) and one in the NTD (serine 77 in RARα).

    “Studies from our laboratory demonstrated that RARs are phosphorylated at two serine residues, one in the LBD (serine 369 in RAR ␣ ) and the other one in the NTD (serine 77 in RAR ␣ ) ( 130, 131 ) ( Fig. 2A ).”
  • The RARγ subtype is also phosphorylated at the LBD and at the NTD.

    “The RAR ␥ subtype is also phosphorylated at the LBD and at the NTD ( 131, 133 ), but whether it results from the same cascade as above is under investigation.”

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Rochette-Egly, C.
Venue
Molecular Endocrinology
Published
1995-07-01
Volume
9
Issue
7
Pages
860-871
ISSN
0888-8809 (ISSN-L)
OpenAlex
W2093523090
Cited by
124
References
46
Citations by year
2024: 1 · 2023: 3 · 2021: 2 · 2019: 2 · 2018: 1 · 2016: 2 · 2015: 4 · 2014: 5 · 2013: 4 · 2012: 3
FWCI
3.20
Type
journal article
Language
en
Open access
Locations
  • Molecular Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Funders
  • Association pour la Recherche sur le Cancer
  • Institut National de la Santé et de la Recherche Médicale
  • Centre National de la Recherche Scientifique
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
retinoic acid receptor alpha, protein kinase A, phosphorylation sites, forskolin, retinoid X receptor alpha, transcriptional activation, retinoic acid response element, F9 cells, cell differentiation, cyclic AMP
MeSH terms
Retinoic Acid Receptor alpha, Amino Acid Sequence, Animals, Base Sequence, Binding Sites, Cell Line, Molecular Sequence Data, Phosphorylation, Protein Kinase C, Transcriptional Activation, Point Mutation, Gene Transfer Techniques, Receptors, Retinoic Acid

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review