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 language | English |
|---|---|
| Pages (from-to) | 4482-4492 |
| Number of pages | 11 |
| Journal | Molecular and Cellular Biology |
| Volume | 32 |
| Issue number | 21 |
| DOIs | |
| Publication status | Published - 2012 Nov 1 |
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ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
Cite this
HtrA1 is a novel antagonist controlling fibroblast growth factor (FGF) signaling via cleavage of FGF8. / Kim, Goo Young; Kim, Ho Young; Kim, Hyun Taek; Moon, Jeong Mi; Kim, Cheol Hee; Kang, Seong Man; Rhim, Hyangshuk.
In: Molecular and Cellular Biology, Vol. 32, No. 21, 01.11.2012, p. 4482-4492.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - HtrA1 is a novel antagonist controlling fibroblast growth factor (FGF) signaling via cleavage of FGF8
AU - Kim, Goo Young
AU - Kim, Ho Young
AU - Kim, Hyun Taek
AU - Moon, Jeong Mi
AU - Kim, Cheol Hee
AU - Kang, Seong Man
AU - Rhim, Hyangshuk
PY - 2012/11/1
Y1 - 2012/11/1
N2 - 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.
AB - 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.
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U2 - 10.1128/MCB.00872-12
DO - 10.1128/MCB.00872-12
M3 - Article
C2 - 22949504
AN - SCOPUS:84868682994
VL - 32
SP - 4482
EP - 4492
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 21
ER -