PMID- 11073973
OWN - NLM
STAT- MEDLINE
DCOM- 20001219
LR  - 20240407
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 20
IP  - 23
DP  - 2000 Dec
TI  - 8-Bromo-cyclic AMP induces phosphorylation of two sites in SRC-1 that facilitate 
      ligand-independent activation of the chicken progesterone receptor and are 
      critical for functional cooperation between SRC-1 and CREB binding protein.
PG  - 8720-30
AB  - Elevation of intracellular 8-bromo-cyclic AMP (cAMP) can activate certain steroid 
      receptors and enhance the ligand-dependent activation of most receptors. During 
      ligand-independent activation of the chicken progesterone receptor (cPR(A)) with 
      the protein kinase A (PKA) activator, 8-bromo-cAMP, we found no alteration in 
      cPR(A) phosphorylation (W. Bai, B. G. Rowan, V. E. Allgood, B. W. O'Malley, and 
      N. L. Weigel, J. Biol. Chem. 272:10457-10463, 1997). To determine if other 
      receptor-associated cofactors were targets of cAMP-dependent signaling pathways, 
      we examined the phosphorylation of steroid receptor coactivator 1 (SRC-1). We 
      detected a 1.8-fold increase in SRC-1 phosphorylation in transfected COS-1 cells 
      incubated with 8-bromo-cAMP. Phosphorylation was increased on two 
      mitogen-activated protein kinase (MAPK) sites, threonine 1179 and serine 1185. 
      PKA did not phosphorylate these sites in vitro. However, blockage of PKA activity 
      in COS-1 cells with the PKA inhibitor (PKI) prevented the 8-bromo-cAMP-mediated 
      phosphorylation of these sites. Incubation of COS-1 cells with 8-bromo-cAMP 
      resulted in activation of the MAPK pathway, as determined by Western blotting 
      with antibodies to the phosphorylated (active) form of Erk-1/2, suggesting an 
      indirect pathway to SRC-1 phosphorylation. Mutation of threonine 1179 and serine 
      1185 to alanine in COS-1 cells coexpressing cPR(A) and the GRE(2)E1bCAT reporter 
      resulted in up to a 50% decrease in coactivation during both ligand-independent 
      activation and ligand-dependent activation. This was due, in part, to loss of 
      functional cooperation between SRC-1 and CREB binding protein for coactivation of 
      cPR(A). This is the first demonstration of cross talk between a signaling pathway 
      and specific phosphorylation sites in a nuclear receptor coactivator that can 
      regulate steroid receptor activation.
FAU - Rowan, B G
AU  - Rowan BG
AD  - Department of Molecular and Cellular Biology, Baylor College of Medicine, 
      Houston, Texas 77030, USA.
FAU - Garrison, N
AU  - Garrison N
FAU - Weigel, N L
AU  - Weigel NL
FAU - O'Malley, B W
AU  - O'Malley BW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Nuclear Proteins)
RN  - 0 (Phosphopeptides)
RN  - 0 (Receptors, Progesterone)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 23583-48-4 (8-Bromo Cyclic Adenosine Monophosphate)
RN  - 2ZD004190S (Threonine)
RN  - 452VLY9402 (Serine)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - EC 2.3.1.48 (CREB-Binding Protein)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 1)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - 8-Bromo Cyclic Adenosine Monophosphate/*pharmacology
MH  - Animals
MH  - CREB-Binding Protein
MH  - Chickens
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - Histone Acetyltransferases
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Models, Genetic
MH  - Nuclear Proteins/*metabolism
MH  - Nuclear Receptor Coactivator 1
MH  - Peptide Mapping
MH  - Phosphopeptides
MH  - Phosphorylation
MH  - Progesterone/pharmacology
MH  - Protein Binding
MH  - Receptors, Progesterone/*metabolism
MH  - Recombinant Proteins/metabolism
MH  - Serine/metabolism
MH  - Signal Transduction
MH  - Threonine/metabolism
MH  - Trans-Activators/*metabolism
MH  - Transcription Factors/genetics/*metabolism
MH  - Transcriptional Activation
PMC - PMC86491
EDAT- 2000/11/14 11:00
MHDA- 2001/02/28 10:01
PMCR- 2000/12/01
CRDT- 2000/11/14 11:00
PHST- 2000/11/14 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/11/14 11:00 [entrez]
PHST- 2000/12/01 00:00 [pmc-release]
AID - 1233 [pii]
AID - 10.1128/MCB.20.23.8720-8730.2000 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2000 Dec;20(23):8720-30. doi: 10.1128/MCB.20.23.8720-8730.2000.