Regulation of transferrin receptor cycling by protein kinase C is independent of receptor phosphorylation at serine 24 in Swiss 3T3 fibroblasts
Department of Biochemistry
Animals; Cells, Cultured; Clone Cells; Fibroblasts; Homeostasis; Humans; Kinetics; Mice; Mutation; Phosphorylation; Platelet-Derived Growth Factor; Protein Kinase C; Receptors, Transferrin; *Serine; Tetradecanoylphorbol Acetate
Life Sciences | Medicine and Health Sciences
Treatment of Swiss 3T3 fibroblasts with tumor-promoting phorbol diester or with platelet-derived growth factor caused the phosphorylation of the transferrin receptor by protein kinase C (Ca2+/phospholipid-dependent enzyme) at serine 24 and increased the cell surface expression of the transferrin receptor. The hypothesis that the regulation of transferrin receptor cycling by protein kinase C is causally related to the phosphorylation of the receptor at serine 24 was critically tested. Site-directed mutagenesis of the human transferrin receptor cDNA was used to substitute serine 24 with threonine or alanine residues in order to create phosphorylation defective receptors. Wild-type and mutated transferrin receptors were expressed in Swiss 3T3 fibroblasts using the retrovirus vector pZipNeoSV (X). These receptors were functionally active and caused the receptor-mediated endocytosis of diferric transferrin. Incubation of the fibroblasts with phorbol diester caused the phosphorylation of the wild-type (Ser-24) human transferrin receptor, but this treatment did not result in the phosphorylation of the mutated (Ala-24 and Thr-24) receptors. The cycling of the phosphorylation defective receptors was regulated by phorbol diester and platelet-derived growth factor in a manner similar to that observed for the wild-type receptor. We conclude that the regulation of transferrin receptor cycling by protein kinase C is independent of receptor phosphorylation at serine 24 in Swiss 3T3 fibroblasts.
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Citation: J Biol Chem. 1987 Nov 25;262(33):16041-7.
The Journal of biological chemistry
Davis, Roger J. and Meisner, Herman, "Regulation of transferrin receptor cycling by protein kinase C is independent of receptor phosphorylation at serine 24 in Swiss 3T3 fibroblasts" (1987). Open Access Articles. 904.