Casein kinase 2β as a novel enhancer of activin-like receptor-1 signaling

Nam Y. Lee, John C. Haney, Julie Sogani, Gerard C. Blobe

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

ALK-1 is a transforming growth factor β (TGF-β) superfamily receptor that is predominantly expressed in endothelial cells and is essential for angiogenesis, as demonstrated by the embryonic lethal phentoype when targeted for deletion in mice and its mutation in the human disease hereditary hemorrhagic telangiectasia. Although ALK-1 and the endothelial-specific TGF-β superfamily coreceptor, endoglin, form a heteromeric complex and bind similar TGF-β superfamily ligands, their signaling mechanisms remain poorly characterized. Here we report the identification of CK2β, the regulatory subunit of protein kinase CK2, as a novel enhancer of ALK-1 signaling. The cytoplasmic domain of ALK-1 specifically binds to CK2β in vitro and in vivo. NAAIRS mutagenesis studies define amino acid sequences 181-199 of CK2β and 207-212 of ALK-1 as the interaction domains, respectively. The ALK-1/CK2β interaction specifically enhanced Smad1/5/8 phosphorylation and ALK-1-mediated reporter activation in response to TGF-β1 and BMP-9 treatment. In a reciprocal manner, siRNA-mediated silencing of endogenous CK2β inhibited TGF-β1 and BMP-9-stimulated Smad1/5/8 phosphorylation and ALK-1-mediated reporter activation. Functionally, CK2β enhanced the ability of activated or ligand-stimulated ALK-1 to inhibit endothelial cell migration. Similarly, ALK-1 and CK2β antagonized endothelial tubule formation in Matrigel. These studies support CK2β as an important regulator of ALK-1 signaling and ALK-1-mediated functions in endothelial cells.

Original languageEnglish (US)
Pages (from-to)3712-3721
Number of pages10
JournalFASEB Journal
Volume23
Issue number11
DOIs
StatePublished - 2009
Externally publishedYes

Keywords

  • Angiogenesis
  • Bone morphogenetic protein
  • Endothelial cell biology
  • Migration
  • TGF-β superfamily signaling

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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