PMID- 10383391
OWN - NLM
STAT- MEDLINE
DCOM- 19990727
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 27
DP  - 1999 Jul 2
TI  - Hyperphosphorylation of the retinoid X receptor alpha by activated c-Jun
      NH2-terminal kinases.
PG  - 18932-41
AB  - The nuclear receptor mouse retinoid X receptor alpha (mRXRalpha) was shown to be 
      constitutively phosphorylated in its NH2-terminal A/B region, which contains
      potential phosphorylation sites for proline-directed Ser/Thr kinases. Mutants for
      each putative site were generated and overexpressed in transfected COS-1 cells.
      Constitutively phosphorylated residues identified by tryptic phosphopeptide
      mapping included serine 22 located in the A1 region that is specific to the
      RXRalpha1 isoform. Overexpression and UV activation of the stress-activated
      kinases, c-Jun NH2-terminal kinases 1 and 2 (JNK1 and JNK2), hyperphosphorylated 
      RXRalpha, resulting in a marked decrease in its electrophoretic mobility. This
      inducible hyperphosphorylation involved three residues (serines 61 and 75 and
      threonine 87) in the B region of RXRalpha and one residue (serine 265) in the
      ligand binding domain (E region). Binding assays performed in vitro with purified
      recombinant proteins demonstrated that JNKs did not interact with RXRalpha but
      bound to its heterodimeric partners, retinoic acid receptors alpha and gamma
      (RARalpha and RARgamma). Hyperphosphorylation by JNKs did not affect the
      transactivation properties of either RXRalpha homodimers or RXRalpha/RARalpha
      heterodimers in transfected cultured cells.
FAU - Adam-Stitah, S
AU  - Adam-Stitah S
AD  - Institut de Genetique et de Biologie Moleculaire et Cellulaire,
      CNRS/INSERM/ULP/College de France, BP 163, 67404 Illkirch Cedex, CU de
      Strasbourg, France.
FAU - Penna, L
AU  - Penna L
FAU - Chambon, P
AU  - Chambon P
FAU - Rochette-Egly, C
AU  - Rochette-Egly C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Nuclear Proteins)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 2ZD004190S (Threonine)
RN  - 5688UTC01R (Tretinoin)
RN  - 9DLQ4CIU6V (Proline)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.24 (Mitogen-Activated Protein Kinase 9)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - COS Cells
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cells, Cultured
MH  - Genes, Reporter
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 9
MH  - *Mitogen-Activated Protein Kinases
MH  - Mutagenesis, Site-Directed
MH  - Nuclear Proteins/*metabolism
MH  - Phosphorylation
MH  - Proline/metabolism
MH  - Protein Kinases/metabolism
MH  - Rabbits
MH  - Receptors, Retinoic Acid/genetics/*metabolism
MH  - Retinoid X Receptors
MH  - Structure-Activity Relationship
MH  - Threonine/metabolism
MH  - Transcription Factors/genetics/*metabolism
MH  - Transfection
MH  - Tretinoin/pharmacology
MH  - Ultraviolet Rays
EDAT- 1999/06/26 00:00
MHDA- 1999/06/26 00:01
CRDT- 1999/06/26 00:00
PHST- 1999/06/26 00:00 [pubmed]
PHST- 1999/06/26 00:01 [medline]
PHST- 1999/06/26 00:00 [entrez]
AID - 10.1074/jbc.274.27.18932 [doi]
AID - S0021-9258(19)74103-9 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Jul 2;274(27):18932-41. doi: 10.1074/jbc.274.27.18932.