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The prodomain of BMP4 is necessary and sufficient to generate stable BMP4/7 heterodimers with enhanced bioactivity in vivo.
Neugebauer, Judith M; Kwon, Sunjong; Kim, Hyung-Seok; Donley, Nathan; Tilak, Anup; Sopory, Shailaja; Christian, Jan L.
Afiliação
  • Neugebauer JM; Departments of Neurobiology and Anatomy and.
  • Kwon S; Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University School of Medicine, Portland, OR 97239-3098.
  • Kim HS; Departments of Neurobiology and Anatomy and.
  • Donley N; Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University School of Medicine, Portland, OR 97239-3098.
  • Tilak A; Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University School of Medicine, Portland, OR 97239-3098.
  • Sopory S; Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University School of Medicine, Portland, OR 97239-3098.
  • Christian JL; Departments of Neurobiology and Anatomy and Internal Medicine, Division of Hematology and Hematologic Malignancies, University of Utah, Salt Lake City, UT 84132-3401; and jan.christian@neuro.utah.edu.
Proc Natl Acad Sci U S A ; 112(18): E2307-16, 2015 May 05.
Article em En | MEDLINE | ID: mdl-25902523
Bone morphogenetic proteins 4 and 7 (BMP4 and BMP7) are morphogens that signal as either homodimers or heterodimers to regulate embryonic development and adult homeostasis. BMP4/7 heterodimers exhibit markedly higher signaling activity than either homodimer, but the mechanism underlying the enhanced activity is unknown. BMPs are synthesized as inactive precursors that dimerize and are then cleaved to generate both the bioactive ligand and prodomain fragments, which lack signaling activity. Our study reveals a previously unknown requirement for the BMP4 prodomain in promoting heterodimer activity. We show that BMP4 and BMP7 precursor proteins preferentially or exclusively form heterodimers when coexpressed in vivo. In addition, we show that the BMP4 prodomain is both necessary and sufficient for generation of stable heterodimeric ligands with enhanced activity and can enable homodimers to signal in a context in which they normally lack activity. Our results suggest that intrinsic properties of the BMP4 prodomain contribute to the relative bioactivities of homodimers versus heterodimers in vivo. These findings have clinical implications for the use of BMPs as regenerative agents for the treatment of bone injury and disease.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteína Morfogenética Óssea 4 / Proteína Morfogenética Óssea 7 Limite: Animals / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteína Morfogenética Óssea 4 / Proteína Morfogenética Óssea 7 Limite: Animals / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article