Internalization of IgE receptors on rat basophilic leukemic cells by phorbol ester. Comparison with endocytosis induced by receptor aggregation.
Phorbol myristate acetate (PMA) can induce a rapid and significant decrease in the expression of IgE receptors on RBL-2H3 cells. Fluorescence microscopy confirmed that the down-regulation is due to internalization of receptors. The endocytotic response to PMA shares several characteristics with endocytosis induced by immunochemical aggregation of surface-bound monomeric IgE: the rates of internalization both have a t1/2 of about 5 min, a maximum of 35% of the surface-bound IgE can be endocytosed by the action of PMA (50% by receptor aggregation), endocytosis is sustained for at least up to 60 min, neither stimulus requires extracellular Ca2+ and endocytosis induced by either stimulus is an active process, i.e., is dependent on temperature and cellular energy. Biochemical studies revealed some differences between the endocytotic responses to the two stimuli. After prolonged treatment of cells with dexamethasone, only endocytosis induced by PMA is inhibited. Cells depleted of protein kinase C by prolonged exposure to PMA can sustain a significant endocytotic response to aggregation of IgE receptors, but become completely desensitized to PMA. These data suggest that different biochemical pathways mediate the signals from the two stimuli and that protein kinase C is directly involved in endocytosis induced by PMA but does not have a major role in endocytosis induced by receptor aggregation.
Ra
C
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Section of Chemical Immunology Arthritis and Rheumatism Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, Bethesda, MD 20892.
Furuichi
K
K
Rivera
J
J
Mullins
J M
JM
Isersky
C
C
White
K N
KN
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D015638:Cytochalasin D / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects*; D007073:Immunoglobulin E / Q000276:immunology; D015471:Leukemia, Basophilic, Acute / Q000276:immunology*; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D011961:Receptors, Fc / Q000378:metabolism*; D017455:Receptors, IgE; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000944:Antigens, Differentiation, B-Lymphocyte; D004075:Diglycerides; D011961:Receptors, Fc; D017455:Receptors, IgE; D015638:Cytochalasin D; D007073:Immunoglobulin E; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate