Protein kinase-C-induced down-regulation of calcitonin receptors and calcitonin-activated adenylate cyclase in T47D and BEN cells.

Abstract:

:T47D human breast cancer cells and BEN human lung cancer cells were preincubated with the tumor-promoting phorbol ester phorbol 12-myristate 13-acetate (PMA). In both cell lines there was a decrease in the binding of 125I-labeled salmon calcitonin ([125I]sCT) which was dependent on the dose and time of exposure to PMA. The effect on binding comprised at least two components: the apparent affinity for binding of [125I]sCT was decreased by PMA, and the rate of internalization of bound [125I]sCT was increased more than 2-fold in the presence of PMA. By using dinitrophenol to inhibit cellular metabolic energy and, therefore, receptor internalization, the PMA effects on receptor affinity were dissociated from those on endocytosis. The effects on binding were reflected in a decreased stimulation by sCT of adenylate cyclase activity. This was specific for the calcitonin receptor system, since PMA had no effect on prostaglandin-E2-stimulated adenylate cyclase in the T47D cell. Protein kinase-C (PKC) was implicated in the inhibitory effects of PMA on both binding and adenylate cyclase activation, since inhibition was reduced by simultaneous incubation with the PKC inhibitors H7 and H8. These results suggest that PKC is capable of mediating down-regulation of the CT receptor, and this is most likely by phosphorylation of the receptor itself or an associated protein.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Findlay DM,Michelangeli VP,Robinson PJ

doi

10.1210/endo-125-5-2656

subject

Has Abstract

pub_date

1989-11-01 00:00:00

pages

2656-63

issue

5

eissn

0013-7227

issn

1945-7170

journal_volume

125

pub_type

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