Tyrosine Kinases but Not cAMP-Dependent Protein Kinase Mediate the Induction of Leukocyte Alkaline Phosphatase by Granulocyte-Colony-Stimulating Factor and Retinoic Acid in Acute Promyelocytic Leukemia Cells

M. Gianni, M. L. Calzi, M. Terao, A. Rambaldi, E. Garattini

Research output: Contribution to journalArticle

Abstract

Leukocyte alkaline phosphatase (LAP) is synergistically induced by the combination of all-trans retinoic acid (ATRA) and granulocyte-colony-stimulating factor (G-CSF) in acute promyelocytic leukemia (APL) cells (Gianni′ M. et al., Blood 83: 1909-1921, 1994). The role of cAMP and tyrosine kinases in the induction of LAP was investigated. In the APL cell line NB4, adenosine-3′: 5′-monophosphothioate, cyclic, Rp isomer, a reversible inhibitor of cAMP-dependent protein kinase (PKA), has no effect on the induction of LAP enzymatic activity and mRNA triggered by ATRA + G-CSF, in conditions where this compound completely blocks the upregulation of LAP transcript caused by the combination of the PKA agonist, dibutyryl-cAMP (db-cAMP), and ATRA. Challenge of NB4 cells with G-CSF, dbcAMP and ATRA causes a much higher induction of LAP relative to that observed in the presence of ATRA + G-CSF or ATRA + dbcAMP. Treatment of NB4 with ATRA and G-CSF results in increases in tile tyrosine phosphorylation of several proteins. In the presence of the cytokine and the retinoid, tyrosine kinase inhibitors decrease LAP enzymatic activity and mRNA.

Original languageEnglish
Pages (from-to)846-854
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume208
Issue number2
DOIs
Publication statusPublished - Mar 17 1995

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology
  • Biophysics
  • Biochemistry

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