Activin A induces erythroid gene expressions and inhibits mitogenic cytokine-mediated K562 colony formation by activating p38 MAPK

Huei M. Huang, Huei Y. Chiou, Ju Ling Chang

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Activin A, a member of the transforming growth factor (TGF)-β superfamily, is involved in the regulation of erythroid differentiation. Previous studies have shown that activin A inhibited the colony-forming activity of mouse Friend erythroleukemia cells, however, the mechanism remains unknown. First, we show herein that activin A induced the expression and activated the promoters of α-globin and ζ-globin in K562 cells, confirming that activin A induces erythroid differentiation in K562 cells. The p38 mitogen activated protein kinase (MAPK) inhibitor, SB203580, inhibited and the extracellular signal regulated kinase (ERK) inhibitor, PD98059, enhanced the expression and promoter activities of α-globin and ζ-globin by activin A, indicating that p38 MAPK and ERK are crucial for activin A-induced erythroid genes expression. Second, SB203580 inhibited the inhibitory effect of activin A on the colony-forming activity of K562 cells using the methylcellulose colony assay, indicating that activin A inhibits K562 colony formation by activating p38 MAPK. In addition, mitogenic cytokines SCF, IL-3, and GM-CSF induced colony formation of K562 cells that could be inhibited by PD98059 or enhanced by SB203580, respectively, indicating that these mitogenic cytokines induce K562 colony formation by activating ERK and inactivating p38 MAPK. Furthermore, activin A reduced the induction effect of these mitogenic cytokines on K562 colony formation in a dose-dependent manner. The inhibition of p38 MAPK reverted the inhibitory effect of activin A on mitogenic cytokine-mediated K562 colony formation. We conclude that activin A can regulate the same pathway via p38 MAPK to coordinate cell proliferation and differentiation of K562 cells.

Original languageEnglish
Pages (from-to)789-797
Number of pages9
JournalJournal of Cellular Biochemistry
Volume98
Issue number4
DOIs
Publication statusPublished - Jul 1 2006

Fingerprint

p38 Mitogen-Activated Protein Kinases
Gene expression
Cytokines
Gene Expression
K562 Cells
Globins
Extracellular Signal-Regulated MAP Kinases
activin A
Leukemia, Erythroblastic, Acute
Methylcellulose
Interleukin-3
Cell proliferation
Transforming Growth Factors
Protein Kinase Inhibitors
Granulocyte-Macrophage Colony-Stimulating Factor
Cell Differentiation
Assays
Cell Proliferation

Keywords

  • Activin A
  • ERK
  • Globin gene
  • GM-CSF
  • IL-3
  • p38 MAPK
  • SCF

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Activin A induces erythroid gene expressions and inhibits mitogenic cytokine-mediated K562 colony formation by activating p38 MAPK. / Huang, Huei M.; Chiou, Huei Y.; Chang, Ju Ling.

In: Journal of Cellular Biochemistry, Vol. 98, No. 4, 01.07.2006, p. 789-797.

Research output: Contribution to journalArticle

@article{ff1a72c92fcd46cca2981b69b3feca7a,
title = "Activin A induces erythroid gene expressions and inhibits mitogenic cytokine-mediated K562 colony formation by activating p38 MAPK",
abstract = "Activin A, a member of the transforming growth factor (TGF)-β superfamily, is involved in the regulation of erythroid differentiation. Previous studies have shown that activin A inhibited the colony-forming activity of mouse Friend erythroleukemia cells, however, the mechanism remains unknown. First, we show herein that activin A induced the expression and activated the promoters of α-globin and ζ-globin in K562 cells, confirming that activin A induces erythroid differentiation in K562 cells. The p38 mitogen activated protein kinase (MAPK) inhibitor, SB203580, inhibited and the extracellular signal regulated kinase (ERK) inhibitor, PD98059, enhanced the expression and promoter activities of α-globin and ζ-globin by activin A, indicating that p38 MAPK and ERK are crucial for activin A-induced erythroid genes expression. Second, SB203580 inhibited the inhibitory effect of activin A on the colony-forming activity of K562 cells using the methylcellulose colony assay, indicating that activin A inhibits K562 colony formation by activating p38 MAPK. In addition, mitogenic cytokines SCF, IL-3, and GM-CSF induced colony formation of K562 cells that could be inhibited by PD98059 or enhanced by SB203580, respectively, indicating that these mitogenic cytokines induce K562 colony formation by activating ERK and inactivating p38 MAPK. Furthermore, activin A reduced the induction effect of these mitogenic cytokines on K562 colony formation in a dose-dependent manner. The inhibition of p38 MAPK reverted the inhibitory effect of activin A on mitogenic cytokine-mediated K562 colony formation. We conclude that activin A can regulate the same pathway via p38 MAPK to coordinate cell proliferation and differentiation of K562 cells.",
keywords = "Activin A, ERK, Globin gene, GM-CSF, IL-3, p38 MAPK, SCF",
author = "Huang, {Huei M.} and Chiou, {Huei Y.} and Chang, {Ju Ling}",
year = "2006",
month = "7",
day = "1",
doi = "10.1002/jcb.20713",
language = "English",
volume = "98",
pages = "789--797",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - Activin A induces erythroid gene expressions and inhibits mitogenic cytokine-mediated K562 colony formation by activating p38 MAPK

AU - Huang, Huei M.

AU - Chiou, Huei Y.

AU - Chang, Ju Ling

PY - 2006/7/1

Y1 - 2006/7/1

N2 - Activin A, a member of the transforming growth factor (TGF)-β superfamily, is involved in the regulation of erythroid differentiation. Previous studies have shown that activin A inhibited the colony-forming activity of mouse Friend erythroleukemia cells, however, the mechanism remains unknown. First, we show herein that activin A induced the expression and activated the promoters of α-globin and ζ-globin in K562 cells, confirming that activin A induces erythroid differentiation in K562 cells. The p38 mitogen activated protein kinase (MAPK) inhibitor, SB203580, inhibited and the extracellular signal regulated kinase (ERK) inhibitor, PD98059, enhanced the expression and promoter activities of α-globin and ζ-globin by activin A, indicating that p38 MAPK and ERK are crucial for activin A-induced erythroid genes expression. Second, SB203580 inhibited the inhibitory effect of activin A on the colony-forming activity of K562 cells using the methylcellulose colony assay, indicating that activin A inhibits K562 colony formation by activating p38 MAPK. In addition, mitogenic cytokines SCF, IL-3, and GM-CSF induced colony formation of K562 cells that could be inhibited by PD98059 or enhanced by SB203580, respectively, indicating that these mitogenic cytokines induce K562 colony formation by activating ERK and inactivating p38 MAPK. Furthermore, activin A reduced the induction effect of these mitogenic cytokines on K562 colony formation in a dose-dependent manner. The inhibition of p38 MAPK reverted the inhibitory effect of activin A on mitogenic cytokine-mediated K562 colony formation. We conclude that activin A can regulate the same pathway via p38 MAPK to coordinate cell proliferation and differentiation of K562 cells.

AB - Activin A, a member of the transforming growth factor (TGF)-β superfamily, is involved in the regulation of erythroid differentiation. Previous studies have shown that activin A inhibited the colony-forming activity of mouse Friend erythroleukemia cells, however, the mechanism remains unknown. First, we show herein that activin A induced the expression and activated the promoters of α-globin and ζ-globin in K562 cells, confirming that activin A induces erythroid differentiation in K562 cells. The p38 mitogen activated protein kinase (MAPK) inhibitor, SB203580, inhibited and the extracellular signal regulated kinase (ERK) inhibitor, PD98059, enhanced the expression and promoter activities of α-globin and ζ-globin by activin A, indicating that p38 MAPK and ERK are crucial for activin A-induced erythroid genes expression. Second, SB203580 inhibited the inhibitory effect of activin A on the colony-forming activity of K562 cells using the methylcellulose colony assay, indicating that activin A inhibits K562 colony formation by activating p38 MAPK. In addition, mitogenic cytokines SCF, IL-3, and GM-CSF induced colony formation of K562 cells that could be inhibited by PD98059 or enhanced by SB203580, respectively, indicating that these mitogenic cytokines induce K562 colony formation by activating ERK and inactivating p38 MAPK. Furthermore, activin A reduced the induction effect of these mitogenic cytokines on K562 colony formation in a dose-dependent manner. The inhibition of p38 MAPK reverted the inhibitory effect of activin A on mitogenic cytokine-mediated K562 colony formation. We conclude that activin A can regulate the same pathway via p38 MAPK to coordinate cell proliferation and differentiation of K562 cells.

KW - Activin A

KW - ERK

KW - Globin gene

KW - GM-CSF

KW - IL-3

KW - p38 MAPK

KW - SCF

UR - http://www.scopus.com/inward/record.url?scp=33745608475&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745608475&partnerID=8YFLogxK

U2 - 10.1002/jcb.20713

DO - 10.1002/jcb.20713

M3 - Article

C2 - 16440334

AN - SCOPUS:33745608475

VL - 98

SP - 789

EP - 797

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 4

ER -