Regulation of Myeloid-Specific Calcium Binding Protein Synthesis by Cytosolic Protein Kinase C

Abstract

Two calcium binding proteins, MRP-8 and MRP-14, are specifically synthesized in human myeloid cells. This paper shows that Me₂SO, all-trans-retinoic acid (RA) and 1α, 25-dihydroxyvitamin D₃, (1α, 25(OH)₂D₃), but not 12-O-tetradecanoyl phorbol-13-acetate (PMA) are potent inducers of MRP-8/14 protein complex in human leukemic cells. Transforming growth factor-β1 (TGF-βl) is shown to enhance the inductive effect of RA and 1α, 25(OH)₂D₃. We have examined the possibility that MRP expression is regulated through the protein kinase pathway. Both cytosolic and membrane-bound protein kinase C (PKC) activities increased during differentiation by RA and 1α, 25(OH)₂D₃. PMA-treatment led to a decrease of cytosolic PKC activity and an increase of membrane-bound PKC activity in the presence of these differentiation inducers, while PMA alone resulted in low cytosolic and high membrane-bound PKC activities. PKC inhibitor H7 inhibited MRP synthesis in HL-60 cells treated with RA and 1α, 25(OH)₂D₃. These results suggest that cytosolic PKC activity may be involved in a stimulatory pathway of MRP synthesis and that protein phosphorylation reactions may play important roles in MRP expression during myelocytic differentiation.