Autocrine signaling of platelet-derived growth factor regulates disabled-2 expression during megakaryocytic differentiation of K562 cells

Ching Ping Tseng, Pam Chang, Chien Ling Huang, Ju Chien Cheng, Shy Shin Chang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Platelet-derived growth factor (PDGF) is involved in megakaryocytopoiesis and is secreted into the culture medium during megakaryocytic differentiation of human leukemic cells. We investigate whether PDGF plays a role in the regulation of the adapter protein Disabled-2 (DAB2) that expresses abundantly in platelets and megakaryocytes. Western blot analysis revealed that conditioned medium from 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated, megakaryocytic differentiating K562 cells upregulated DAB2 expression. DAB2 induction and megakaryocytic differentiation was abrogated when cells were co-treated with the PDGF receptor inhibitor STI571 or when the conditioned medium was derived from TPA-plus STI571-treated cells. Although the level of PDGF mRNA was not altered by STI571, an approximate 44% decrease in PDGF in the conditioned medium was observed. Consistent with these findings, interfering PDGF signaling by PDGF neutralization antibody or dominant negative PDGF receptors attenuated DAB2 expression. Accordingly, transfection of an expression plasmid encoding secreted PDGF upregulated DAB2. This study shows for the first time that PDGF autocrine signaling regulates DAB2 expression during megakaryocytic differentiation.

Original languageEnglish
Pages (from-to)4395-4401
Number of pages7
JournalFEBS Letters
Volume579
Issue number20
DOIs
Publication statusPublished - Aug 15 2005
Externally publishedYes

Fingerprint

Autocrine Communication
K562 Cells
Platelet-Derived Growth Factor
Conditioned Culture Medium
Platelet-Derived Growth Factor Receptors
Tetradecanoylphorbol Acetate
Acetates
Cells
Thrombopoiesis
Megakaryocytes
Platelets
Transfection
Culture Media
Plasmids
Blood Platelets
Western Blotting
Messenger RNA

Keywords

  • Disabled-2
  • Megakaryocytic differentiation
  • Platelet-derived growth factor
  • STI571

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Autocrine signaling of platelet-derived growth factor regulates disabled-2 expression during megakaryocytic differentiation of K562 cells. / Tseng, Ching Ping; Chang, Pam; Huang, Chien Ling; Cheng, Ju Chien; Chang, Shy Shin.

In: FEBS Letters, Vol. 579, No. 20, 15.08.2005, p. 4395-4401.

Research output: Contribution to journalArticle

Tseng, Ching Ping ; Chang, Pam ; Huang, Chien Ling ; Cheng, Ju Chien ; Chang, Shy Shin. / Autocrine signaling of platelet-derived growth factor regulates disabled-2 expression during megakaryocytic differentiation of K562 cells. In: FEBS Letters. 2005 ; Vol. 579, No. 20. pp. 4395-4401.
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