Tumor-promoting phorbol esters suppress receptor-stimulated inositol phospholipid degradation and Ca2+ mobilization in mouse lymphocytes.

Abstract:

:Anti-immunoglobulin antibodies (anti-Ig) provoke the rapid breakdown of phosphatidylinositol bisphosphate (PIP2), elevation of cytoplasmic Ca2+ levels ([Ca2+]i) and activation of protein kinase C (PKC) in B lymphocytes. Tumor-promoting phorbol esters, like phorbol myristate acetate, also activate PKC, but inhibit anti-Ig-induced B cell proliferation. To investigate the basis of the latter effect, we studied the influence of phorbol esters on PIP2 degradation and [Ca2+]i in murine B cells. The results show that PKC-activating phorbol esters cause marked inhibition of anti-Ig-stimulated PIP2 breakdown and Ca2+ mobilization. In addition, these agents inhibit concanavalin A-provoked Ca2+ influx, lower resting cytoplasmic Ca2+ levels and reduce ionophore-induced Ca2+ influx in B cells. Apparently, PKC stimulation causes feedback inhibition of receptor signalling, not only by suppressing PIP2 degradation, but also by exerting additional complex effects on the control of [Ca2+]i in B cells. It is, however, not clear how these findings relate to the anti-proliferative effects of phorbol esters on B cells.

journal_name

Eur J Immunol

authors

Bijsterbosch MK,Klaus GG

doi

10.1002/eji.1830170119

subject

Has Abstract

pub_date

1987-01-01 00:00:00

pages

113-8

issue

1

eissn

0014-2980

issn

1521-4141

journal_volume

17

pub_type

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