Effects of protein kinase modulators on transferrin receptor expression in human leukaemic HL-60 cells

FEBS Lett. 1995 May 29;365(2-3):137-40. doi: 10.1016/0014-5793(95)00442-c.


The mRNA of transferrin receptor (TfR) is constitutively expressed in proliferating human leukaemic HL-60 cells. Treatment of HL-60 cells with phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, or dibutyryl-cyclic AMP (dbcAMP), a protein kinase A (PKA) activator, resulted in a 90% decrease in the level of TfR mRNA. Inhibition of TfR mRNA expression induced by 10 nM PMA and 100 microM dbcAMP was abolished by prior incubation of cells with 0.1-1.0 microM GF109203X, a PKC-specific inhibitor, and 1-10 microM H-89, a PKA-specific inhibitor, respectively. The blocking effects of GF109203X and H-89 were dose-dependent and complete at the highest concentrations of the inhibitors used. Although treatment of cells with GF109203X or H-89 alone did not alter the constitutive expression of TfR mRNA, incubation of cells with 30-100 nM staurosporine, a wide-spectrum protein kinase inhibitor, resulted in suppression of the constitutive expression of TfR mRNA in a dose-dependent manner. These results suggest that (i) the down-regulation of TfR mRNA expression during the differentiation of HL-60 cells can be mediated by activation of either PKC or PKA; (ii) the constitutive expression of TfR mRNA in proliferating HL-60 cells is staurosporine-sensitive and is probably maintained by protein kinase(s) other than PKC and PKA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology
  • Bucladesine / pharmacology*
  • Cell Division / drug effects
  • Cell Line
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • DNA, Neoplasm / biosynthesis
  • Enzyme Activation
  • Gene Expression / drug effects*
  • Humans
  • Indoles / pharmacology
  • Isoquinolines / pharmacology
  • Leukemia, Promyelocytic, Acute
  • Maleimides / pharmacology
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinases / metabolism*
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • Receptors, Transferrin / biosynthesis*
  • Staurosporine
  • Sulfonamides*
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Thymidine / metabolism
  • Tumor Cells, Cultured


  • Alkaloids
  • DNA, Neoplasm
  • Indoles
  • Isoquinolines
  • Maleimides
  • RNA, Messenger
  • Receptors, Transferrin
  • Sulfonamides
  • Bucladesine
  • Protein Kinases
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • Staurosporine
  • bisindolylmaleimide I
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
  • Tetradecanoylphorbol Acetate
  • Thymidine