TY - JOUR
T1 - Divergent cytokine receptors support terminal red blood cell differentiation in vtvo
AU - Mikami, Aki
AU - You, Yun
AU - Liu, Kathleen D.
AU - Thomas, Liza
AU - Longmore', Gregory D.
AU - Ralph, H.
N1 - Funding Information:
This study is a contribution due to GDR Marges, Actions Marges, ANR YOCMAL, INSU-DYETI, CNRS-PICS Oman and CNRS-PICS Yemen. We thank Philippe Patriat for stimulating discussions and also Nadine Ellouz-Zimmermann. We are grateful to the Ministry of Commerce and Industry, Directorate of Minerals of Muscat, Ministry of Oil and Gas, GSMRB, French Embassies in Sana?a and in Muscat for their support during the project.
PY - 1998
Y1 - 1998
N2 - Erythropoietin (Epo) is required for red blood cell development; however, it has been difficult to determine experimentally whether the role is instructive or supportive. Chimeric receptors were constructed by replacing the cytoplasmic tail of a constitutively active erythropoietin receptor (cEpoR) with tails of other cytokine receptors. The extracellular domain of cEpoR contains an R129C point substitution that causes constitutive, covalent receptor homodimerization and continuous transmission of signals in the absence of Epo. Through retroviral transduction these ligand-independent activated chimeric receptors were expressed in primary erythroid progenitors in culture and in vivo. Chimeric receptors with cytoplasmic tails from the granulocyte colony stimulating factor receptor or from the growth hormone receptor supported erythroid colony development. A chimeric receptor with a c-mpl tail was partially active. Infection of NIHSwiss mice with these recombinant viruses in the presence of replication competent Rauscher helper virus caused splenomegaly and elevation in hernatocrit. Therefore, EpoR specific signals are not required for the differentiation of erythrocytes. Rather, cytokine-dependent signaling provides a supportive function for erythroid differentiation.
AB - Erythropoietin (Epo) is required for red blood cell development; however, it has been difficult to determine experimentally whether the role is instructive or supportive. Chimeric receptors were constructed by replacing the cytoplasmic tail of a constitutively active erythropoietin receptor (cEpoR) with tails of other cytokine receptors. The extracellular domain of cEpoR contains an R129C point substitution that causes constitutive, covalent receptor homodimerization and continuous transmission of signals in the absence of Epo. Through retroviral transduction these ligand-independent activated chimeric receptors were expressed in primary erythroid progenitors in culture and in vivo. Chimeric receptors with cytoplasmic tails from the granulocyte colony stimulating factor receptor or from the growth hormone receptor supported erythroid colony development. A chimeric receptor with a c-mpl tail was partially active. Infection of NIHSwiss mice with these recombinant viruses in the presence of replication competent Rauscher helper virus caused splenomegaly and elevation in hernatocrit. Therefore, EpoR specific signals are not required for the differentiation of erythrocytes. Rather, cytokine-dependent signaling provides a supportive function for erythroid differentiation.
UR - http://www.scopus.com/inward/record.url?scp=33748624612&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:33748624612
SN - 0301-472X
VL - 26
SP - 763
JO - Experimental Hematology
JF - Experimental Hematology
IS - 8
ER -