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http://purl.uniprot.org/citations/14662325http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/14662325http://www.w3.org/2000/01/rdf-schema#comment"

Objective

To determine the role of the c-terminal half of c-Mpl in Mpl-L-induced myeloprotection and the importance of Stat5 isoforms in the survival signaling pathways induced by Mpl ligand.

Materials and methods

Delta60-Mpl knockin mice, Stat5a(-/-)/b(-/-), Stat5a(-/-), and Stat5b(-/-) mice and wild-type (WT) controls were given a lethal myelosuppressive regimen: 80 mg/kg carboplatin intravenously followed by 7.5 or 6.5 Gy 137Cs total-body irradiation. A single dose of PEG-rmMGDF (65 microg/kg) was intravenously injected immediately after myelosuppression. Mice survival and blood counts were monitored for 22 days posttreatment.

Results

Knockin Delta60-Mpl mice lacking the c-terminal half of the intracellular domain of c-Mpl show reduced ability of Mpl-L to prevent lethal myelosuppression and an impaired thrombopoietic response to exogenous c-Mpl ligand. The survival of Mpl-L-treated Stat5a(-/-)/b(-/-) mice exposed to the lethal myelosuppressive regimen was substantially compromised compared to that of WT mice. Reduced survival of Stat5a(-/-)/b(-/-) mice was due to more severe hematopoietic suppression. Deletion of Stat5a did not result in a defect in hematopoietic recovery. In contrast, Mpl-L-treated Stat5b-deficient mice demonstrated significantly delayed hematopoietic recovery compared to WT controls.

Conclusions

Myeloprotective signaling transduced by the terminal 60 amino acids of the intracellular domain of c-Mpl is essential for complete protection from lethal myelosuppression provided by Mpl-L. Our studies differentiate the functions of Stat5 isoforms in hematopoietic stress and reveal a pivotal role of Stat5b in Mpl-L-induced hematopoietic recovery in this lethal myelosuppression model."xsd:string
http://purl.uniprot.org/citations/14662325http://purl.org/dc/terms/identifier"doi:10.1016/j.exphem.2003.09.002"xsd:string
http://purl.uniprot.org/citations/14662325http://purl.uniprot.org/core/author"Jackson C.W."xsd:string
http://purl.uniprot.org/citations/14662325http://purl.uniprot.org/core/author"Pestina T.I."xsd:string
http://purl.uniprot.org/citations/14662325http://purl.uniprot.org/core/date"2003"xsd:gYear
http://purl.uniprot.org/citations/14662325http://purl.uniprot.org/core/name"Exp Hematol"xsd:string
http://purl.uniprot.org/citations/14662325http://purl.uniprot.org/core/pages"1198-1205"xsd:string
http://purl.uniprot.org/citations/14662325http://purl.uniprot.org/core/title"Differential role of Stat5 isoforms in effecting hematopoietic recovery induced by Mpl-ligand in lethally myelosuppressed mice."xsd:string
http://purl.uniprot.org/citations/14662325http://purl.uniprot.org/core/volume"31"xsd:string
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