Title
Insulin-like growth factor I and epidermal growth factor regulate the expression of transferrin receptors at the cell surface by distinct mechanisms
UMMS Affiliation
Department of Biochemistry; Program in Molecular Medicine
Publication Date
1987-09-25
Document Type
Article
Subjects
Carcinoma, Squamous Cell; Cell Membrane; Epidermal Growth Factor; Exocytosis; Humans; Insulin-Like Growth Factor I; Iron; Kinetics; Models, Biological; Receptors, Transferrin; Somatomedins
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
The transferrin receptor cycles rapidly between cell surface and endosomal membrane compartments. Treatment of cultured cells with epidermal growth factor (EGF) or insulin-like growth factor I (IGF-I) at 37 degrees C causes a rapid redistribution of transferrin receptors from an intracellular compartment to the cell surface. The effects of EGF and IGF-I on the kinetics of the cycling of the transferrin receptor in A431 human epidermoid carcinoma cells were compared. The primary site of EGF action was found to be an increase in the rate of transferrin receptor exocytosis. The exocytotic rate constant was measured to be 0.11 min-1 in control cells and 0.33 min-1 in EGF-treated cells. In contrast, IGF-I was found to increase the cell surface expression of transferrin receptors by causing a small increase in the rate of exocytosis (from 0.11 to 0.17 min-1) and a decrease in the rate of endocytosis (from 0.33 to 0.24 min-1). It is concluded that the mechanisms for EGF and IGF-I action to increase the cell surface expression of the transferrin receptor are distinct. A kinetic model of the cycling of the transferrin receptor based on experimentally determined rate constants is presented. The model predicts that a consequence of IGF-I action on transferrin receptor cycling is to decrease the apparent Km for the uptake of diferric transferrin by cells. This prediction is confirmed by direct measurement of the accumulation of 59Fe-labeled diferric transferrin by A431 cells. These data demonstrate that the accumulation of iron by cultured cells is a complex function of the rate of cycling of the transferrin receptor and that this process is under acute regulation by growth factors.
Source
J Biol Chem. 1987 Sep 25;262(27):13126-34.
Journal/Book/Conference Title
The Journal of biological chemistry
Related Resources
PubMed ID
3498714
Repository Citation
Davis RJ, Faucher M, Racaniello LK, Carruthers A, Czech MP. (1987). Insulin-like growth factor I and epidermal growth factor regulate the expression of transferrin receptors at the cell surface by distinct mechanisms. Open Access Publications by UMass Chan Authors. Retrieved from https://escholarship.umassmed.edu/oapubs/906