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Selective phosphorylations of the SRC-3/AIB1 coactivator integrate genomic reponses to multiple cellular signaling

Ray-Chang Wu1, Jun Qin, Ping Yi

  • 1Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

Molecular Cell
|September 24, 2004
PubMed

Insights

Steroid receptor coactivator SRC-3 phosphorylation sites regulate distinct cellular functions. Specific phosphorylation patterns dictate SRC-3

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Gene Regulation

Background:

  • SRC-3 (Steroid Receptor Coactivator-3) is a key transcriptional coactivator involved in various cellular processes.
  • Phosphorylation is a known regulatory mechanism for SRC-3 activity, but its role in pathway-specific functions is unclear.

Purpose of the Study:

  • To identify functional in vivo phosphorylation sites on SRC-3.
  • To investigate how different phosphorylation patterns of SRC-3 mediate distinct signaling pathway outputs.

Main Methods:

  • Identification of six functional in vivo SRC-3 phosphorylation sites.
  • Analysis of SRC-3 phosphorylation requirements for coactivation of estrogen receptors, androgen receptors, and NF-kappaB.
  • Assessment of SRC-3 phosphorylation in TNF-alpha-induced IL-6 gene expression and MEF oncogenic transformation.

Main Results:

  • All six identified SRC-3 phosphorylation sites are essential for coactivating estrogen and androgen receptors.
  • Not all sites are required for NF-kappaB coactivation.
  • Distinct phosphorylation site combinations regulate IL-6 gene induction and oncogenic transformation, mediated by differential protein-protein interactions.

Conclusions:

  • Specific phosphorylation events on SRC-3 enable pathway selectivity.
  • Differentially phosphorylated SRC-3 interacts with distinct downstream partners to regulate gene expression and cellular functions.
  • SRC-3 acts as a tunable integrator of diverse signaling pathways through regulated phosphorylation.

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