Transmembrane Protein Aptamer Induces Cooperative Signaling by the EPO Receptor and the Cytokine Receptor ß-Common Subunit.
iScience
; 17: 167-181, 2019 Jul 26.
Article
en En
| MEDLINE
| ID: mdl-31279934
ABSTRACT
The erythropoietin receptor (EPOR) plays an essential role in erythropoiesis and other cellular processes by forming distinct signaling complexes composed of EPOR homodimers or hetero-oligomers between the EPOR and another receptor, but the mechanism of heteroreceptor assembly and signaling is poorly understood. We report here a 46-residue, artificial transmembrane protein aptamer, designated ELI-3, that binds and activates the EPOR and induces growth factor independence in murine BaF3 cells expressing the EPOR. ELI-3 requires the transmembrane domain and JAK2-binding sites of the EPOR for activity, but not the cytoplasmic tyrosines that mediate canonical EPOR signaling. Instead, ELI-3-induced proliferation and activation of JAK/STAT signaling requires the transmembrane and cytoplasmic domains of the cytokine receptor ß-common subunit (ßcR) in addition to the EPOR. Moreover, ELI-3 fails to induce erythroid differentiation of primary human hematopoietic progenitor cells but inhibits nonhematopoietic cell death induced by serum withdrawal.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
IScience
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos