抄録
The erythropoietin receptor (EpoR) is required for the proliferation and survival of committed erythroid lineage cells. Previous studies have utilized receptor mutations to show the requirement for the distal half of the cytoplasmic domain of the EpoR and receptor tyrosines for activation of signaling pathways potentially critical to Epo function. To extend these studies to in vivo erythropoiesis, we have created two mutant strains of mice. One strain (H) contains a truncation of the distal half of the cytoplasmic domain, while the second strain (HM) contains the same truncation as well as the mutation of the residual tyrosine (Y343) to a phenylalanine. Strikingly, both strains of mice are viable, with only slight alterations in constitutive erythropoiesis or in in vitro assays of red cell lineage function. Challenging H mutant mice with continuous injections of Epo results in an erythrocytosis that is not seen in HM mice. The results demonstrate that neither the distal region nor receptor tyrosines are essential for in vivo EpoR function, but contribute to receptor function in a subtle manner.
| 元の言語 | English |
|---|---|
| ページ（範囲） | 3156-3166 |
| ページ数 | 11 |
| ジャーナル | EMBO Journal |
| 巻 | 20 |
| 発行部数 | 12 |
| DOI | |
| 出版物ステータス | Published - 2001 6 15 |
| 外部発表 | Yes |
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ASJC Scopus subject areas
- Genetics
- Cell Biology
これを引用
The distal region and receptor tyrosines of the Epo receptor are non-essential for in vivo erythropoiesis. / Zang, Heesuk; Sato, Ken; Nakajima, Hideaki; McKay, Catriona; Ney, Paul A.; Ihle, James N.
：: EMBO Journal, 巻 20, 番号 12, 15.06.2001, p. 3156-3166.研究成果: Article
}
TY - JOUR
T1 - The distal region and receptor tyrosines of the Epo receptor are non-essential for in vivo erythropoiesis
AU - Zang, Heesuk
AU - Sato, Ken
AU - Nakajima, Hideaki
AU - McKay, Catriona
AU - Ney, Paul A.
AU - Ihle, James N.
PY - 2001/6/15
Y1 - 2001/6/15
N2 - The erythropoietin receptor (EpoR) is required for the proliferation and survival of committed erythroid lineage cells. Previous studies have utilized receptor mutations to show the requirement for the distal half of the cytoplasmic domain of the EpoR and receptor tyrosines for activation of signaling pathways potentially critical to Epo function. To extend these studies to in vivo erythropoiesis, we have created two mutant strains of mice. One strain (H) contains a truncation of the distal half of the cytoplasmic domain, while the second strain (HM) contains the same truncation as well as the mutation of the residual tyrosine (Y343) to a phenylalanine. Strikingly, both strains of mice are viable, with only slight alterations in constitutive erythropoiesis or in in vitro assays of red cell lineage function. Challenging H mutant mice with continuous injections of Epo results in an erythrocytosis that is not seen in HM mice. The results demonstrate that neither the distal region nor receptor tyrosines are essential for in vivo EpoR function, but contribute to receptor function in a subtle manner.
AB - The erythropoietin receptor (EpoR) is required for the proliferation and survival of committed erythroid lineage cells. Previous studies have utilized receptor mutations to show the requirement for the distal half of the cytoplasmic domain of the EpoR and receptor tyrosines for activation of signaling pathways potentially critical to Epo function. To extend these studies to in vivo erythropoiesis, we have created two mutant strains of mice. One strain (H) contains a truncation of the distal half of the cytoplasmic domain, while the second strain (HM) contains the same truncation as well as the mutation of the residual tyrosine (Y343) to a phenylalanine. Strikingly, both strains of mice are viable, with only slight alterations in constitutive erythropoiesis or in in vitro assays of red cell lineage function. Challenging H mutant mice with continuous injections of Epo results in an erythrocytosis that is not seen in HM mice. The results demonstrate that neither the distal region nor receptor tyrosines are essential for in vivo EpoR function, but contribute to receptor function in a subtle manner.
KW - Cytokine signaling
KW - Erythropoiesis
KW - Erythropoietin
KW - Jak2 kinase
KW - Receptor
UR - http://www.scopus.com/inward/record.url?scp=0035876167&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035876167&partnerID=8YFLogxK
U2 - 10.1093/emboj/20.12.3156
DO - 10.1093/emboj/20.12.3156
M3 - Article
C2 - 11406592
AN - SCOPUS:0035876167
VL - 20
SP - 3156
EP - 3166
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 12
ER -