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Regulation of ALK-1 signaling by the nuclear receptor LXRbeta.

Publication ,  Journal Article
Mo, J; Fang, SJ; Chen, W; Blobe, GC
Published in: J Biol Chem
December 27, 2002

The transforming growth factor beta (TGF-beta) receptor, ALK-1, is expressed specifically on endothelial cells and is essential for angiogenesis, as demonstrated by its targeted deletion in mice and its mutation in the human disease hereditary hemorrhagic telangiectasia. Although ALK-1 and another endothelial-specific TGF-beta receptor, endoglin, both bind TGF-beta with identical isoform specificity and form a complex together, neither has been shown to signal in response to TGF-beta, and the mechanism by which these receptors signal in endothelial cells remains unknown. Here we report the identification of the nuclear receptor liver X receptor beta (LXRbeta) as a modulator/mediator of ALK-1 signaling. The cytoplasmic domain of ALK-1 specifically binds to LXRbeta in vitro and in vivo. Expression of activated ALK-1 results in translocation of LXRbeta from the nuclear compartment to the cytoplasmic compartment. The interaction of activated ALK-1 with LXRbeta in the cytoplasmic compartment results in the specific phosphorylation of LXRbeta by ALK-1, primarily on serine residues. LXRbeta subsequently modulates signaling by ALK-1 and the closely related TGF-beta receptor, ALK-2, as demonstrated by specific and potent inhibition of ALK-1- and ALK-2-mediated transcriptional responses, establishing LXRbeta as a potential modulator/mediator of ALK-1/ALK-2 signaling.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

December 27, 2002

Volume

277

Issue

52

Start / End Page

50788 / 50794

Location

United States

Related Subject Headings

  • Transfection
  • Signal Transduction
  • Saccharomyces cerevisiae
  • Recombinant Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Protein Transport
  • Phosphorylation
  • Orphan Nuclear Receptors
  • Organ Specificity
  • Molecular Sequence Data
 

Citation

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Mo, J., Fang, S. J., Chen, W., & Blobe, G. C. (2002). Regulation of ALK-1 signaling by the nuclear receptor LXRbeta. J Biol Chem, 277(52), 50788–50794. https://doi.org/10.1074/jbc.M210376200
Mo, Jinyao, Shijing J. Fang, Wei Chen, and Gerard C. Blobe. “Regulation of ALK-1 signaling by the nuclear receptor LXRbeta.J Biol Chem 277, no. 52 (December 27, 2002): 50788–94. https://doi.org/10.1074/jbc.M210376200.
Mo J, Fang SJ, Chen W, Blobe GC. Regulation of ALK-1 signaling by the nuclear receptor LXRbeta. J Biol Chem. 2002 Dec 27;277(52):50788–94.
Mo, Jinyao, et al. “Regulation of ALK-1 signaling by the nuclear receptor LXRbeta.J Biol Chem, vol. 277, no. 52, Dec. 2002, pp. 50788–94. Pubmed, doi:10.1074/jbc.M210376200.
Mo J, Fang SJ, Chen W, Blobe GC. Regulation of ALK-1 signaling by the nuclear receptor LXRbeta. J Biol Chem. 2002 Dec 27;277(52):50788–50794.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

December 27, 2002

Volume

277

Issue

52

Start / End Page

50788 / 50794

Location

United States

Related Subject Headings

  • Transfection
  • Signal Transduction
  • Saccharomyces cerevisiae
  • Recombinant Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Protein Transport
  • Phosphorylation
  • Orphan Nuclear Receptors
  • Organ Specificity
  • Molecular Sequence Data