Constitutive phosphorylation of GATA-1 at serine²⁶ attenuates the colony-forming activity of erythrocyte-committed progenitors.

We previously reported that IL-3 signaling induces phosphorylation of GATA-1 at the serine²⁶ position, which contributes to IL-3-mediated anti-apoptotic response. Here, we demonstrate that phosphorylation of GATA-1 at serine²⁶ is also transiently induced in cells of the erythroid lineage (primary er...

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Autores principales:	Kou-Ray Lin, Chung-Leung Li, Jeffrey Jong-Young Yen, Hsin-Fang Yang-Yen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ad8cfdd99d944b77bd154baba98a238f
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spelling	oai:doaj.org-article:ad8cfdd99d944b77bd154baba98a238f2021-11-18T07:44:34ZConstitutive phosphorylation of GATA-1 at serine²⁶ attenuates the colony-forming activity of erythrocyte-committed progenitors.1932-620310.1371/journal.pone.0064269https://doaj.org/article/ad8cfdd99d944b77bd154baba98a238f2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23717580/?tool=EBIhttps://doaj.org/toc/1932-6203We previously reported that IL-3 signaling induces phosphorylation of GATA-1 at the serine²⁶ position, which contributes to IL-3-mediated anti-apoptotic response. Here, we demonstrate that phosphorylation of GATA-1 at serine²⁶ is also transiently induced in cells of the erythroid lineage (primary erythroblasts and erythrocyte-committed progenitors [EPs]) by erythropoietin (EPO), the principal cytokine regulating erythropoiesis. To examine whether phosphorylation of GATA-1 at serine²⁶ would have any impact on erythropoiesis, mutant mice carrying either a glutamic acid (GATA-1(S26E)) or alanine (GATA-1(S26A)) substitution at serine²⁶ were generated. Neither GATA-1(S26E) nor GATA-1(S26A) mice showed any significant difference from control mice in peripheral blood cell composition under either steady state or stress conditions. The erythroblast differentiation in both mutant mice also appeared to be normal. However, a moderate reduction in the CFU-E progenitor population was consistently observed in the bone marrow of GATA-1(S26E), but not GATA-1(S26A) mice, suggesting that such defect was compensated for within the bone marrow. Surprisingly, reduced CFU-E progenitor population in GATA-1(S26E) mice was mainly due to EPO-induced growth suppression of GATA-1(S26E) EPs, albeit in the absence of EPO these cells manifested a survival advantage. Further analyses revealed that EPO-induced growth suppression of GATA-1(S26E) EPs was largely due to the proliferation block resulted from GATA-1(S26E)-mediated transcriptional activation of the gene encoding the cell cycle inhibitor p21(Waf1/Cip1). Taken together, these results suggest that EPO-induced transient phosphorylation of GATA-1 at serine²⁶ is dispensable for erythropoiesis. However, failure to dephosphorylate this residue following its transient phosphorylation significantly attenuates the colony-forming activity of EPs.Kou-Ray LinChung-Leung LiJeffrey Jong-Young YenHsin-Fang Yang-YenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e64269 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kou-Ray Lin Chung-Leung Li Jeffrey Jong-Young Yen Hsin-Fang Yang-Yen Constitutive phosphorylation of GATA-1 at serine²⁶ attenuates the colony-forming activity of erythrocyte-committed progenitors.
description	We previously reported that IL-3 signaling induces phosphorylation of GATA-1 at the serine²⁶ position, which contributes to IL-3-mediated anti-apoptotic response. Here, we demonstrate that phosphorylation of GATA-1 at serine²⁶ is also transiently induced in cells of the erythroid lineage (primary erythroblasts and erythrocyte-committed progenitors [EPs]) by erythropoietin (EPO), the principal cytokine regulating erythropoiesis. To examine whether phosphorylation of GATA-1 at serine²⁶ would have any impact on erythropoiesis, mutant mice carrying either a glutamic acid (GATA-1(S26E)) or alanine (GATA-1(S26A)) substitution at serine²⁶ were generated. Neither GATA-1(S26E) nor GATA-1(S26A) mice showed any significant difference from control mice in peripheral blood cell composition under either steady state or stress conditions. The erythroblast differentiation in both mutant mice also appeared to be normal. However, a moderate reduction in the CFU-E progenitor population was consistently observed in the bone marrow of GATA-1(S26E), but not GATA-1(S26A) mice, suggesting that such defect was compensated for within the bone marrow. Surprisingly, reduced CFU-E progenitor population in GATA-1(S26E) mice was mainly due to EPO-induced growth suppression of GATA-1(S26E) EPs, albeit in the absence of EPO these cells manifested a survival advantage. Further analyses revealed that EPO-induced growth suppression of GATA-1(S26E) EPs was largely due to the proliferation block resulted from GATA-1(S26E)-mediated transcriptional activation of the gene encoding the cell cycle inhibitor p21(Waf1/Cip1). Taken together, these results suggest that EPO-induced transient phosphorylation of GATA-1 at serine²⁶ is dispensable for erythropoiesis. However, failure to dephosphorylate this residue following its transient phosphorylation significantly attenuates the colony-forming activity of EPs.
format	article
author	Kou-Ray Lin Chung-Leung Li Jeffrey Jong-Young Yen Hsin-Fang Yang-Yen
author_facet	Kou-Ray Lin Chung-Leung Li Jeffrey Jong-Young Yen Hsin-Fang Yang-Yen
author_sort	Kou-Ray Lin
title	Constitutive phosphorylation of GATA-1 at serine²⁶ attenuates the colony-forming activity of erythrocyte-committed progenitors.
title_short	Constitutive phosphorylation of GATA-1 at serine²⁶ attenuates the colony-forming activity of erythrocyte-committed progenitors.
title_full	Constitutive phosphorylation of GATA-1 at serine²⁶ attenuates the colony-forming activity of erythrocyte-committed progenitors.
title_fullStr	Constitutive phosphorylation of GATA-1 at serine²⁶ attenuates the colony-forming activity of erythrocyte-committed progenitors.
title_full_unstemmed	Constitutive phosphorylation of GATA-1 at serine²⁶ attenuates the colony-forming activity of erythrocyte-committed progenitors.
title_sort	constitutive phosphorylation of gata-1 at serine²⁶ attenuates the colony-forming activity of erythrocyte-committed progenitors.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/ad8cfdd99d944b77bd154baba98a238f
work_keys_str_mv	AT kouraylin constitutivephosphorylationofgata1atserine26attenuatesthecolonyformingactivityoferythrocytecommittedprogenitors AT chungleungli constitutivephosphorylationofgata1atserine26attenuatesthecolonyformingactivityoferythrocytecommittedprogenitors AT jeffreyjongyoungyen constitutivephosphorylationofgata1atserine26attenuatesthecolonyformingactivityoferythrocytecommittedprogenitors AT hsinfangyangyen constitutivephosphorylationofgata1atserine26attenuatesthecolonyformingactivityoferythrocytecommittedprogenitors
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Constitutive phosphorylation of GATA-1 at serine²⁶ attenuates the colony-forming activity of erythrocyte-committed progenitors.

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