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Effects of protein kinase modulators on transferrin receptor expression in human leukaemic HL‐60 cells
Author(s) -
Lok C.N.,
Chan K.-F.J.,
Loh T.T.
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00442-c
Subject(s) - protein kinase c , staurosporine , transferrin receptor , activator (genetics) , protein kinase a , phorbol , protein kinase inhibitor , messenger rna , microbiology and biotechnology , kinase , biology , receptor , chemistry , biochemistry , gene
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 μM dbcAMP was abolished by prior incubation of cells with 0.1–1.0 μM GF109203X, a PKC‐specific inhibitor, and 1–10 μM 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.