PMID- 10660621
OWN - NLM
STAT- MEDLINE
DCOM- 20000316
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 6
DP  - 2000 Feb 11
TI  - Phosphorylation of steroid receptor coactivator-1. Identification of the 
      phosphorylation sites and phosphorylation through the mitogen-activated protein 
      kinase pathway.
PG  - 4475-83
AB  - Steroid receptor coactivator-1 (SRC-1) is a member of a coactivator family that 
      enhance the activation of the steroid/nuclear receptor superfamily of 
      ligand-stimulated transcription factors. To study the regulation of SRC-1 by 
      signaling pathways in the cell, the major phosphorylation sites of SRC-1 were 
      identified in COS-1 cells using a combination of in vivo labeling with 
      [(32)P]H(3)PO(4), modified manual Edman degradation, phosphoamino acid analysis, 
      endoproteinase digestion, and mutagenesis of the SRC-1 phosphorylation sites. 
      Seven phosphorylation sites were identified in SRC-1: serine 372, serine 395, 
      serine 517, serine 569, serine 1033, threonine 1179, and serine 1185. All the 
      sites contained consensus sequences for the serine/threonine-proline-directed 
      family of protein kinases, and two sites (serine 395 and threonine 1179) 
      contained a perfect consensus sequence for the mitogen-activated protein kinase 
      family (Erk-1 and Erk-2). Furthermore, Erk-2 phosphorylated threonine 1179 and 
      serine 1185 (and to a lesser extent, serine 395) in vitro, suggesting the 
      importance of this pathway for SRC-1 regulation. Treatment of cells expressing 
      SRC-1 with epidermal growth factor enhanced the ligand-dependent, progesterone 
      receptor-mediated activation of a target reporter gene. These results identify 
      phosphorylation as a regulatory modification of SRC-1 and provide a basis upon 
      which to identify signaling pathways that regulate SRC-1 function and, 
      consequently, modify steroid/nuclear receptor action.
FAU - Rowan, B G
AU  - Rowan BG
AD  - Department of Molecular and Cellular Biology, Baylor College of Medicine, 
      Houston, Texas 77030, USA.
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  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Phosphopeptides)
RN  - 0 (Receptors, Progesterone)
RN  - 0 (Transcription Factors)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - COS Cells
MH  - Electrophoresis, Gel, Two-Dimensional
MH  - Epidermal Growth Factor/pharmacology
MH  - Genes, Reporter
MH  - Histone Acetyltransferases
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Molecular Sequence Data
MH  - Nuclear Receptor Coactivator 1
MH  - Phosphopeptides/chemistry
MH  - Phosphorylation
MH  - Progesterone/pharmacology
MH  - Receptors, Progesterone/metabolism
MH  - Signal Transduction
MH  - Transcription Factors/chemistry/*metabolism
EDAT- 2000/02/08 09:00
MHDA- 2000/03/18 09:00
CRDT- 2000/02/08 09:00
PHST- 2000/02/08 09:00 [pubmed]
PHST- 2000/03/18 09:00 [medline]
PHST- 2000/02/08 09:00 [entrez]
AID - S0021-9258(18)30857-3 [pii]
AID - 10.1074/jbc.275.6.4475 [doi]
PST - ppublish
SO  - J Biol Chem. 2000 Feb 11;275(6):4475-83. doi: 10.1074/jbc.275.6.4475.