HtrA1 is a novel antagonist controlling fibroblast growth factor (FGF) signaling via cleavage of FGF8

Goo Young Kim, Ho Young Kim, Hyun Taek Kim, Jeong Mi Moon, Cheol Hee Kim, Seong Man Kang, Hyangshuk Rhim

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Accumulating evidence suggests that HtrA1 (high-temperature requirement A1) is involved in modulating crucial cellular processes and implicated in life-threatening diseases, such as cancer and neuropathological disorders; however, the exact functions of this protease in vivo remain unknown. Here, we show that loss of HtrA1 function increases fibroblast growth factor 8 (FGF8) mRNA levels and triggers activation of FGF signaling, resulting in dorsalization in zebrafish embryos. Notably, HtrA1 directly cleaves FGF8 in the extracellular region, and this cleavage results in decreased activation of FGF signaling, which is essential for many physiological processes. Therefore, HtrA1 is indispensable for dorsoventral patterning in early zebrafish embryogenesis and serves as a key upstream regulator of FGF signaling through the control of FGF levels. Furthermore, this study offers insight into new strategies to control human diseases associated with HtrA1 and FGF signaling.

Original languageEnglish
Pages (from-to)4482-4492
Number of pages11
JournalMolecular and Cellular Biology
Volume32
Issue number21
DOIs
Publication statusPublished - 2012 Nov 1

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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