Abstract
The glial cell line-derived neurotrophic factor (GDNF)/RET tyrosine kinase signaling pathway plays crucial roles in the development of the enteric nervous system (ENS) and the kidney. Tyrosine 1062 (Y1062) in RET is an autophosphorylation residue that is responsible for the activation of the PI3K/AKT and RAS/MAPK signaling pathways. Mice lacking signaling via Ret Y1062 show renal hypoplasia and hypoganglionosis of the ENS although the phenotype is milder than the Gdnf- or Ret-deficient mice. Sprouty2 (Spry2) was found to be an antagonist for fibroblast growth factor receptor (FGFR) and acts as an inhibitory regulator of ERK activation. Spry2-deficient mice exhibit hearing loss and enteric nerve hyperplasia. In the present study, we generated Spry2-deficient and Ret Y1062F knock-in (tyrosine 1062 is replaced with phenylalanine) double mutant mice to see if abnormalities of the ENS and kidney, caused by loss of signaling via Ret Y1062, are rescued by a deficiency of Spry2. Double mutant mice showed significant recovery of ureteric bud branching and ENS development in the stomach. These results indicate that Spry2 regulates downstream signaling mediated by GDNF/RET signaling complex in vivo.
| Original language | English |
|---|---|
| Pages (from-to) | 160-168 |
| Number of pages | 9 |
| Journal | Developmental Biology |
| Volume | 349 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2011 Jan 15 |
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Keywords
- Enteric nervous system
- RET tyrosine kinase
- Signal transduction
- Sprouty2
- Ureteric bud branching
ASJC Scopus subject areas
- Developmental Biology
- Cell Biology
- Molecular Biology
Cite this
Loss of Sprouty2 partially rescues renal hypoplasia and stomach hypoganglionosis but not intestinal aganglionosis in Ret Y1062F mutant mice. / Miyamoto, Rieko; Jijiwa, Mayumi; Asai, Masato; Kawai, Kumi; Ishida-Takagishi, Maki; Mii, Shinji; Asai, Naoya; Enomoto, Atsushi; Murakumo, Yoshiki; Yoshimura, Akihiko; Takahashi, Masahide.
In: Developmental Biology, Vol. 349, No. 2, 15.01.2011, p. 160-168.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Loss of Sprouty2 partially rescues renal hypoplasia and stomach hypoganglionosis but not intestinal aganglionosis in Ret Y1062F mutant mice
AU - Miyamoto, Rieko
AU - Jijiwa, Mayumi
AU - Asai, Masato
AU - Kawai, Kumi
AU - Ishida-Takagishi, Maki
AU - Mii, Shinji
AU - Asai, Naoya
AU - Enomoto, Atsushi
AU - Murakumo, Yoshiki
AU - Yoshimura, Akihiko
AU - Takahashi, Masahide
PY - 2011/1/15
Y1 - 2011/1/15
N2 - The glial cell line-derived neurotrophic factor (GDNF)/RET tyrosine kinase signaling pathway plays crucial roles in the development of the enteric nervous system (ENS) and the kidney. Tyrosine 1062 (Y1062) in RET is an autophosphorylation residue that is responsible for the activation of the PI3K/AKT and RAS/MAPK signaling pathways. Mice lacking signaling via Ret Y1062 show renal hypoplasia and hypoganglionosis of the ENS although the phenotype is milder than the Gdnf- or Ret-deficient mice. Sprouty2 (Spry2) was found to be an antagonist for fibroblast growth factor receptor (FGFR) and acts as an inhibitory regulator of ERK activation. Spry2-deficient mice exhibit hearing loss and enteric nerve hyperplasia. In the present study, we generated Spry2-deficient and Ret Y1062F knock-in (tyrosine 1062 is replaced with phenylalanine) double mutant mice to see if abnormalities of the ENS and kidney, caused by loss of signaling via Ret Y1062, are rescued by a deficiency of Spry2. Double mutant mice showed significant recovery of ureteric bud branching and ENS development in the stomach. These results indicate that Spry2 regulates downstream signaling mediated by GDNF/RET signaling complex in vivo.
AB - The glial cell line-derived neurotrophic factor (GDNF)/RET tyrosine kinase signaling pathway plays crucial roles in the development of the enteric nervous system (ENS) and the kidney. Tyrosine 1062 (Y1062) in RET is an autophosphorylation residue that is responsible for the activation of the PI3K/AKT and RAS/MAPK signaling pathways. Mice lacking signaling via Ret Y1062 show renal hypoplasia and hypoganglionosis of the ENS although the phenotype is milder than the Gdnf- or Ret-deficient mice. Sprouty2 (Spry2) was found to be an antagonist for fibroblast growth factor receptor (FGFR) and acts as an inhibitory regulator of ERK activation. Spry2-deficient mice exhibit hearing loss and enteric nerve hyperplasia. In the present study, we generated Spry2-deficient and Ret Y1062F knock-in (tyrosine 1062 is replaced with phenylalanine) double mutant mice to see if abnormalities of the ENS and kidney, caused by loss of signaling via Ret Y1062, are rescued by a deficiency of Spry2. Double mutant mice showed significant recovery of ureteric bud branching and ENS development in the stomach. These results indicate that Spry2 regulates downstream signaling mediated by GDNF/RET signaling complex in vivo.
KW - Enteric nervous system
KW - RET tyrosine kinase
KW - Signal transduction
KW - Sprouty2
KW - Ureteric bud branching
UR - http://www.scopus.com/inward/record.url?scp=78650809394&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78650809394&partnerID=8YFLogxK
U2 - 10.1016/j.ydbio.2010.11.002
DO - 10.1016/j.ydbio.2010.11.002
M3 - Article
VL - 349
SP - 160
EP - 168
JO - Developmental Biology
JF - Developmental Biology
SN - 0012-1606
IS - 2
ER -