PMID- 10608897
OWN - NLM
STAT- MEDLINE
DCOM- 20000208
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 53
DP  - 1999 Dec 31
TI  - Serine 157, a retinoic acid receptor alpha residue phosphorylated by protein
      kinase C in vitro, is involved in RXR.RARalpha heterodimerization and
      transcriptional activity.
PG  - 38225-31
AB  - Retinoic acid (RA) regulation of cellular proliferation and differentiation is
      mediated, at least in part, through two related nuclear receptors, RAR and RXR.
      RA-induced modulation of gene expression leads generally to cellular
      differentiation, whereas stimulation of the protein kinase C (PKC) signaling
      pathway is associated with cellular proliferation. Pursuant to our discovery that
      prolonged activation of PKCs induced a strong decrease in RA responsiveness of a 
      retinoid-inducible reporter gene, we have further investigated the connections
      between these two signaling pathways. We demonstrate that PKC isoforms alpha and 
      gamma are able to phosphorylate human RARalpha (hRARalpha) in vitro on a single
      serine residue located in the extended DNA binding domain (T box). The
      introduction of a negative charge at this position (serine 157) strongly
      decreased hRARalpha transcriptional activity, whereas a similar mutation at other
      PKC consensus phosphorylation sites had no effect. The effect on transcriptional 
      activation was correlated with a decrease in the capacity of hRARalpha to
      heterodimerize with hRXRalpha. Thus hRARalpha is a direct target for PKCalpha and
      gamma, which may control retinoid receptor transcriptional activities during
      cellular proliferation and differentiation.
FAU - Delmotte, M H
AU  - Delmotte MH
AD  - INSERM Unite 459, Faculte de Medecine Henri Warembourg, 1, place de Verdun, 59045
      Lille cedex, France.
FAU - Tahayato, A
AU  - Tahayato A
FAU - Formstecher, P
AU  - Formstecher P
FAU - Lefebvre, P
AU  - Lefebvre P
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 (DNA Primers)
RN  - 0 (RARA protein, human)
RN  - 0 (Rara protein, rat)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoic Acid Receptor alpha)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - DNA Primers
MH  - Dimerization
MH  - HeLa Cells
MH  - Humans
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Phosphorylation
MH  - Protein Kinase C/*metabolism
MH  - Rats
MH  - Receptors, Retinoic Acid/chemistry/genetics/*metabolism
MH  - Retinoic Acid Receptor alpha
MH  - Retinoid X Receptors
MH  - Sequence Homology, Amino Acid
MH  - Serine/chemistry/*metabolism
MH  - Transcription Factors/chemistry/genetics/*metabolism
MH  - *Transcription, Genetic
EDAT- 1999/12/23 00:00
MHDA- 1999/12/23 00:01
CRDT- 1999/12/23 00:00
PHST- 1999/12/23 00:00 [pubmed]
PHST- 1999/12/23 00:01 [medline]
PHST- 1999/12/23 00:00 [entrez]
AID - 10.1074/jbc.274.53.38225 [doi]
AID - S0021-9258(19)53017-4 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Dec 31;274(53):38225-31. doi: 10.1074/jbc.274.53.38225.