Lyn deficiency reduces GATA-1, EKLF and STAT5, and induces extramedullary stress erythropoiesis

E. Ingley; D.J. McCarthy; J.R. Pore; M.K. Sarna; A.S. Adenan; M.J. Wright; W. Erber; P.A. Tilbrook; S.P. Klinken

doi:10.1038/sj.onc.1208199

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Lyn deficiency reduces GATA-1, EKLF and STAT5, and induces extramedullary stress erythropoiesis

Journal article

Peer reviewed

Lyn deficiency reduces GATA-1, EKLF and STAT5, and induces extramedullary stress erythropoiesis

E. Ingley, D.J. McCarthy, J.R. Pore, M.K. Sarna, A.S. Adenan, M.J. Wright, W. Erber, P.A. Tilbrook and S.P. Klinken

Oncogene, Vol.24(3), pp.336-343

2005

DOI: https://doi.org/10.1038/sj.onc.1208199

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Abstract

In vitro studies have implicated the Lyn tyrosine kinase in erythropoietin signaling. In this study, we show that J2E erythroid cells lacking Lyn have impaired signaling and reduced levels of transcription factors STAT5a, EKLF and GATA-1. Since mice lacking STAT5, EKLF or GATA-1 have red cell abnormalities, this study also examined the erythroid compartment of Lyn-/- mice. Significantly, STAT5, EKLF and GATA-1 levels were appreciably lower in Lyn -/- erythroblasts, and the phenotype of Lyn-/- animals was remarkably similar to GATA-Ilow animals. Although young adult Lyn-deficient mice had normal hematocrits, older mice developed anemia. Grossly enlarged erythroblasts and florid erythrophagocytosis were detected in the bone marrow of mice lacking Lyn. Markedly elevated erythroid progenitors and precursor levels were observed in the spleens, but not bone marrow, of Lyn -/- animals indicating that extramedullary erythropoiesis was occurring. These data indicate that Lyn-/- mice display extramedullary stress erythropoiesis to compensate for intrinsic and extrinsic erythroid defects.

Details

Title: Lyn deficiency reduces GATA-1, EKLF and STAT5, and induces extramedullary stress erythropoiesis
Authors/Creators: E. Ingley (Author/Creator) - The University of Western Australia
D.J. McCarthy (Author/Creator) - The University of Western Australia
J.R. Pore (Author/Creator) - The University of Western Australia
M.K. Sarna (Author/Creator) - The University of Western Australia
A.S. Adenan (Author/Creator) - The University of Western Australia
M.J. Wright (Author/Creator) - The University of Western Australia
W. Erber (Author/Creator) - Queen Elizabeth II Medical Centre
P.A. Tilbrook (Author/Creator) - The University of Western Australia
S.P. Klinken (Author/Creator) - The University of Western Australia
Publication Details: Oncogene, Vol.24(3), pp.336-343
Publisher: Nature Publishing Group
Identifiers: 991005541538607891
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.184 Physiology & Metals; 1.184.1030 Erythropoietin Therapy
Web Of Science research areas: Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity; Oncology
ESI research areas: Molecular Biology & Genetics