Journal of Molecular Medicine

, Volume 82, Issue 9, pp 621–628

Stimulation of c-Rel transcriptional activity by PKA catalytic subunit β

  • Shih-Hung Yu
  • Wei-Chung Chiang
  • Hsiu-Ming Shih
  • Kou-Juey Wu
Original Article

Abstract

Nuclear factor κB (NF-κB) is a eukaryotic transcription factor which responds to different extracellular signals. It is involved in immune response, inflammation, and cell proliferation. Increased expression of c-Rel (or its viral homolog v-Rel), one component of the NF-κB factors, induces tumorigenesis in different systems. The activity of NF-κB can be regulated by protein kinase A (PKA) in a cAMP-independent manner. Our previous results showed that c-MYC induces the activity of PKA by inducing the transcription of the gene encoding the PKA catalytic subunit β (PKA-Cβ). Constitutive expression of PKA-Cβ in Rat1a cells induces their transformation. Here we show that CREB is unlikely to be a phosphorylation target of PKA-Cβ as characterized by different cell lines. Electrophoretic mobility shift assays showed that c-Rel is present as a significant component of the NF-κB factors in c-MYC overexpressing status. The transcriptional activity of c-Rel was significantly stimulated by PKA-Cβ. Coactivators p300/CBP are at least partially responsible for the enhanced activation mediated by c-Rel and PKA-Cβ. Interaction between c-Rel and PKA-Cβ was demonstrated using coimmunoprecipitation assays. Immunoprecipitation-in vitro phosphorylation assays showed the direct phosphorylation of c-Rel by PKA-Cβ. These results indicate that c-Rel is a reasonable phosphorylation target of PKA-Cβ, and that the transcriptional activity of c-Rel is stimulated by PKA-Cβ possibly through the interaction with p300/CBP.

Keywords

Nuclear factor kB c-Rel Protein kinase A catalytic subunit β c-MYC Transcription 

Abbreviations

CBP

CREB-binding protein

IκB

Inhibitor factor κB

NF-κB

Nuclear factor κB

PKA

Protein kinase A

SDS-PAGE

Sodium dodecyl sulfate polyacrylamide gel electrophoresis

TC

Tetracycline

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Shih-Hung Yu
    • 1
  • Wei-Chung Chiang
    • 1
  • Hsiu-Ming Shih
    • 2
  • Kou-Juey Wu
    • 1
  1. 1.Institute of BiochemistryNational Yang-Ming UniversityTaipei 112Taiwan
  2. 2.Division of Molecular and Genomic MedicineNational Health Research InstitutesTaipei 115Taiwan

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