Skip to main content

Identification of calcium-modulating cyclophilin ligand (CAML) as transducer of angiotensin II-mediated nuclear factor of activated T cells (NFAT) activation.

Publication ,  Journal Article
Guo, S; Lopez-Ilasaca, M; Dzau, VJ
Published in: J Biol Chem
April 1, 2005

Angiotensin II (Ang II) plays a central role in cardiovascular physiology and disease. Ang II type I receptor (AT1) is thought to mediate most actions of Ang II. A novel AT1 receptor intracellular partner called AT1 receptor-associated protein (ATRAP) was identified, but its exact function has not been elucidated. A yeast two-hybrid screen using ATRAP as bait identified calcium-modulating cyclophilin ligand (CAML) as an ATRAP partner. Yeast two-hybrid and coimmunoprecipitation analysis demonstrated that the N-terminal hydrophilic domain of CAML (amino acids (aa) 1-189) mediates a specific interaction between ATRAP and CAML. Our analysis also showed that aa 40-82 of ATRAP contribute to this interaction. Bioluminescence resonance energy transfer and intracellular colocalization analysis by immunofluorescence in HEK293 cells verified this association within endoplasmic reticulum vesicular structures. Functionally, transcriptional reporter assays and RNA interference ATRAP experiments demonstrated that ATRAP knockdown increased nuclear factor of activated T cells (NFAT) activity. Overexpression of ATRAP decreased Ang II- or CAML-induced NFAT transcriptional activation, whereas an ATRAP-interacting domain of CAML (aa 1-189) sensitized NFAT activation in response to Ang II. These results indicate that CAML is an important signal transducer for the actions of Ang II in regulating the calcineurin-NFAT pathway and suggest that the interaction of CAML with ATRAP may mediate the Ang II actions in vascular physiology.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

April 1, 2005

Volume

280

Issue

13

Start / End Page

12536 / 12541

Location

United States

Related Subject Headings

  • Two-Hybrid System Techniques
  • Transcriptional Activation
  • Transcription, Genetic
  • Transcription Factors
  • Signal Transduction
  • RNA, Small Interfering
  • RNA Interference
  • Protein Structure, Tertiary
  • Protein Binding
  • Plasmids
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Guo, S., Lopez-Ilasaca, M., & Dzau, V. J. (2005). Identification of calcium-modulating cyclophilin ligand (CAML) as transducer of angiotensin II-mediated nuclear factor of activated T cells (NFAT) activation. J Biol Chem, 280(13), 12536–12541. https://doi.org/10.1074/jbc.M500296200
Guo, Shaodong, Marco Lopez-Ilasaca, and Victor J. Dzau. “Identification of calcium-modulating cyclophilin ligand (CAML) as transducer of angiotensin II-mediated nuclear factor of activated T cells (NFAT) activation.J Biol Chem 280, no. 13 (April 1, 2005): 12536–41. https://doi.org/10.1074/jbc.M500296200.
Guo, Shaodong, et al. “Identification of calcium-modulating cyclophilin ligand (CAML) as transducer of angiotensin II-mediated nuclear factor of activated T cells (NFAT) activation.J Biol Chem, vol. 280, no. 13, Apr. 2005, pp. 12536–41. Pubmed, doi:10.1074/jbc.M500296200.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

April 1, 2005

Volume

280

Issue

13

Start / End Page

12536 / 12541

Location

United States

Related Subject Headings

  • Two-Hybrid System Techniques
  • Transcriptional Activation
  • Transcription, Genetic
  • Transcription Factors
  • Signal Transduction
  • RNA, Small Interfering
  • RNA Interference
  • Protein Structure, Tertiary
  • Protein Binding
  • Plasmids