Lyn deficiency reduces GATA-1, EKLF and STAT5, and induces extramedullary stress erythropoiesis.
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-1(low) 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.
Ingley
Evan
E
Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and Centre for Medical Research, The University of Western Australia, WA, Australia.
McCarthy
David J
DJ
Pore
Jessica R
JR
Sarna
Mohinda K
MK
Adenan
Aini S
AS
Wright
Michael J
MJ
Erber
Wendy
W
Tilbrook
Peta A
PA
Klinken
S Peter
SP
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D004900:Erythroblasts / Q000502:physiology; D050981:Erythroid-Specific DNA-Binding Factors; D004920:Erythropoiesis / Q000235:genetics*; D050982:GATA1 Transcription Factor; D005786:Gene Expression Regulation; D006410:Hematopoiesis / Q000235:genetics; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D018345:Mice, Knockout; D008894:Milk Proteins / Q000235:genetics*; D009856:Oncogene Proteins, Viral / Q000172:deficiency / Q000235:genetics; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D016335:Zinc Fingers; D019061:src-Family Kinases / Q000172:deficiency* / Q000235:genetics*
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D051741:Kruppel-Like Transcription Factors; D008894:Milk Proteins; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D050799:STAT5 Transcription Factor; C494093:Stat5a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C080774:erythroid Kruppel-like factor; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases