Lyn kinase promotes erythroblast expansion and late-stage development Journal Article
| Authors: | Karur, V. G.; Lowell, C. A.; Besmer, P.; Agosti, V.; Wojchowski, D. M. |
| Article Title: | Lyn kinase promotes erythroblast expansion and late-stage development |
| Abstract: | 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. |
| Keywords: | mice; protein-tyrosine kinases; src-family kinases; erythropoietin receptor; signaling pathways; negative regulation; deficient; hematopoietic-cells; b-cell development; affinity ige receptor; marrow mast-cells |
| Journal Title: | Blood |
| Volume: | 108 |
| Issue: | 5 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2006-09-01 |
| Start Page: | 1524 |
| End Page: | 1532 |
| Language: | English |
| ACCESSION: | WOS:000240271500022 |
| DOI: | 10.1182/blood-2005-09-008243 |
| PROVIDER: | wos |
| PMCID: | PMC1895506 |
| PUBMED: | 16705093 |
| Notes: | --- - Article - "Source: Wos" |
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