Lyn kinase promotes erythroblast expansion and late-stage development.
Lyn kinase is known to modulate the formation and function of B cells, monocytes, and mast cells. However, Lyn-/- mice also develop erythrosplenomegaly, and cases for both negative and positive erythropoietic actions of Lyn recently have been outlined. In phenylhydrazine-treated Lyn-/- mice, extramedullary splenic erythropoiesis was hyperactivated, but this did not lead to accelerated recovery from anemia. Furthermore, ex vivo analyses of the development of bone marrow-derived Lyn-/- erythroblasts in unique primary culture systems indicated positive roles for Lyn at 2 stages. Late-stage Lyn-/- erythroblasts exhibited deficit Ter119(pos) cell formation, and this was paralleled by increased apoptosis (and decreased Bcl-xL expression). During early development, Lyn-/- erythroblasts accumulated at a Kit(pos)CD71(high) stage, possessed decreased proliferative capacity, and were attenuated in entering an apparent G1/S cell-cycle phase. In proposed compensatory responses, Lyn-/- erythroblasts expressed increased levels of activated Akt and p60-Src and decreased levels of death-associated protein kinase-2. Stat5 activation and Bcl-xL expression, in contrast, were significantly decreased in keeping with decreased survival and developmental potentials. Lyn, therefore, is proposed to function via erythroid cell-intrinsic mechanisms to promote progenitor cell expansion beyond a Kit(pos)CD71(high) stage and to support subsequent late-stage development.
Karur
Vinit G
VG
Maine Medical Center Research Institute, 81 Research Dr, Scarborough, ME 04074, USA.
Lowell
Clifford A
CA
Besmer
Peter
P
Agosti
Valter
V
Wojchowski
Don M
DM
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D001854:Bone Marrow Cells / Q000166:cytology; D002453:Cell Cycle; D002455:Cell Division / Q000502:physiology*; D002470:Cell Survival; D004900:Erythroblasts / Q000166:cytology* / Q000502:physiology*; D006410:Hematopoiesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011990:Receptors, Transferrin / Q000502:physiology; D013163:Splenomegaly / Q000235:genetics; D019089:Stem Cell Factor / Q000502:physiology; D019061:src-Family Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D015703:Antigens, CD; C068126:CD71 antigen; D011990:Receptors, Transferrin; D019089:Stem Cell Factor; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases