Spleen tyrosine kinase mediates the actions of EPO and GM-CSF and coordinates with TGF-β in erythropoiesis

Hua Ching Chang, Duen Yi Huang, Mai Szu Wu, Ching Liang Chu, Shiang Jong Tzeng, Wan Wan Lin

研究成果: 雜誌貢獻文章同行評審

6 引文 斯高帕斯(Scopus)

摘要

Erythropoietin (EPO) and GM-CSF are involved in erythropoiesis, while TGF-β inhibits proliferation but potentiates differentiation of erythroblasts. Since Syk inhibitor may induce anemia side effect in clinic, here we investigated the role of Syk in the biological actions of EPO and GM-CSF in erythropoiesis. In human erythroleukemia cell line TF-1, Syk inhibitor R406 exerts an enhancement effect with TGF-β to decrease cell viability, either in the absence or presence of EPO or GM-CSF. Such effect of R406 results from the reduced cell cycle progression and increased cell apoptosis. Notably, unlike Syk, Src family kinases are not involved in the viability control of TF-1 cells. Signaling studies showed that Syk is required for STAT5 and ERK activation induced by EPO, and Akt and ERK activation induced by GM-CSF. Nevertheless, R406 does not change the Smad2/3 signal caused by TGF-β, and TGF-β neither affects above signal pathways of EPO and GM-CSF. Of note, Syk is constitutively associated with EPOR in plasma membrane and can bind to STAT5 at active status upon EPO stimulation. Furthermore, EPO-induced hemoglobin γ expression was reduced by R406. In BFU-E and CFU-E colony formation assays in Syk-deficient erythroid progenitor cells, we confirmed the essential role of Syk in erythropoiesis mediated by EPO. Taken together, Syk is a novel upstream signaling molecule of EPOR, and contributes to erythroblast proliferation, survival and differentiation.

原文英語
頁(從 - 到)687-696
頁數10
期刊Biochimica et Biophysica Acta - Molecular Cell Research
1864
發行號4
DOIs
出版狀態已發佈 - 四月 1 2017

ASJC Scopus subject areas

  • 分子生物學
  • 細胞生物學

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