The FOP metamorphogene encodes a novel type I receptor that dysregulates BMP signaling

Frederick S. Kaplan, Robert J. Pignolo, Eileen M. Shore

Research output: Contribution to journalReview article

42 Scopus citations

Abstract

The ability of mature organisms to stabilize phenotypes has enormous selective advantage across all phyla, but the mechanisms have been largely unexplored. Individuals with fibrodysplasia ossificans progressiva (FOP), a rare genetic disorder of progressive heterotopic ossification, undergo a pathological metamorphosis in which one normal tissue is transformed into another through a highly regulated process of tissue destruction and phenotype reassignment. This disabling metamorphosis is mediated by the FOP metamorphogene, which encodes a mutant bone morphogenetic protein (BMP) type I receptor that exhibits mild constitutive activity during development and severe episodic dysregulation postnatally. The discovery of the FOP metamorphogene reveals a highly conserved target for drug development and identifies a fundamental defect in the BMP signaling pathway that when triggered by injury and inflammation transforms one tissue into another.

Original languageEnglish (US)
Pages (from-to)399-407
Number of pages9
JournalCytokine and Growth Factor Reviews
Volume20
Issue number5-6
DOIs
StatePublished - Oct 1 2009

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Keywords

  • ACVR1
  • Activin-like kinase 2 (ALK2)
  • BMP signaling
  • Bone morphogenetic protein (BMP) receptor
  • Fibrodysplasia ossificans progressiva
  • Heterotopic ossification
  • Metamorphogene
  • Metamorphosis

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Immunology and Allergy
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

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