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Different sensitivities of neutrophil responses to a selective protein kinase C inhibitor Ro 31-8425; redundancy in signal transduction.

Abstract：

:Previous studies implicating a role for protein kinase C (PKC) in mediating stimulation of cellular responses by physiological agonists have relied on use of non-specific inhibitors or direct stimulation of PKC by phorbol esters. However, much of this evidence is questionable. Here, we have investigated the effects of a potent and selective PKC inhibitor, Ro 31-8425, on three different responses of human neutrophils stimulated by either a physiological agonist, C5a, or a phorbol ester, PMA. The responses studied were superoxide generation, collagenase secretion and adhesion to endothelial cells. In each case, the PMA-stimulated response was more sensitive to inhibition than the C5a-stimulated response. Even the PMA-stimulated responses differed in their sensitivity to inhibition, with superoxide production being the most sensitive and adhesion at least sensitive. The different sensitivities of the PMA stimulated responses suggest that, although activation of PKC stimulates the responses, either different degrees of activation or different isozymes are required for the different responses. The lower sensitivity of the C5a-stimulated responses in each case suggests that PKC activation, if needed at all, is not rate limiting in these signal transduction pathways. These results emphasize the redundancy in intracellular signal transduction.

journal_name

Cell Signal

journal_title

Cellular signalling

authors

Merritt JE,Sullivan JA,Tse J,Wilkinson Se,Nixon JS

doi

10.1016/s0898-6568(96)00097-6

subject

Has Abstract

pub_date

1997-01-01 00:00:00

pages

53-7

issue

1

eissn

0898-6568

issn

1873-3913

pii

S0898656896000976

journal_volume

9

pub_type

杂志文章

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