Erythropoietin induces tyrosine phosphorylation and activation of phospholipase C-γ1 in a human erythropoietin-dependent cell line

Han Yun Ren, Norio Komatsu, Ritsuko Shimizu, Koji Okada, Yasusada Miura

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87 Citations (Scopus)

Abstract

Erythropoietin (Epo) is the major regulator of the proliferation and differentiation of erythroid precursors through interaction with its receptor (Epo-R). Although Epo-R lacks a tyrosine kinase consensus sequence within its intracellular domain, the addition of its ligand to Epo-responsive cells, UT- 7/Epo, induces the rapid and transient tyrosine phosphorylation of 145-, 130- , 80-, and 40-kDa cellular proteins. Tyrosine phosphorylation of these proteins occurred dose- and time-dependently. We showed that the tyrosine phosphorylated 145- kDa protein is identical to phospholipase C-γ1 (PLC- γ1). Tyrosine phosphorylation of this protein is detectable within 30 s and almost reaches the maximum at 1 min. This can last up to 10 min and declines thereafter. Additionally, in Epo-stimulated cells, PLC-γ1 become physically associated with 80- and 40-kDa proteins which have been tyrosine- phosphorylated in response to Epo. The activity of PLC-γ1 was also investigated using inositol 1,4,5-trisphosphate (Ins-P3) as an indicator. We found that stimulation of UT-7/Epo cells with Epo induces a significant accumulation of Ins-P3. This effect is dose-dependent and occurs very rapidly. The production of Ins-P3 can explain the Epo-induced mobilization of calcium from intracellular stores in these cells. These results demonstrate that Epo induces tyrosine phosphorylation and activation of PLC- γ1 to produce Ins-P3 and then it mobilizes calcium from intracellular stores. This signal transduction pathway may play a role in regulating the proliferation of erythroid cells.

Original languageEnglish
Pages (from-to)19633-19638
Number of pages6
JournalJournal of Biological Chemistry
Volume269
Issue number30
Publication statusPublished - 1994 Jul 29
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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