Atypical PKC zeta is activated by ceramide, resulting in coactivation of NF-kappaB/JNK kinase and cell survival.

Abstract:

:Both protein kinase C (PKC) and ceramide play a critical role in cell signaling, but the relationship between PKC and ceramide is unclear. Low concentrations of ceramide were observed to transiently stimulate PKC zeta activity in vitro and in vivo, whereas high doses of ceramide lead to inhibition of PKC zeta. Inhibition of activity was accompanied by enhanced binding of the negative regulator, Par4 to PKC zeta. Treatment of PC12 cells with low doses of ceramide promoted survival in serum-free media and activation of nuclear factor-KB, whereas higher doses (>2.5 microM) resulted in cell death. Overexpression of either aPKC isoform, PKC zeta or iota, resulted in enhanced survival of PC12 cells at high doses of ceramide and in ceramide-stimulated Jun N-terminal kinase (JNK), without any apparent effect on mitogen-activated kinase. These findings support a role for ceramide-induced PKC zeta activity in the control of cell survival signaling via a pathway that also activates JNK kinase.

journal_name

J Neurosci Res

authors

Wang YM,Seibenhener ML,Vandenplas ML,Wooten MW

doi

10.1002/(SICI)1097-4547(19990201)55:3<293::AID-JNR

keywords:

subject

Has Abstract

pub_date

1999-02-01 00:00:00

pages

293-302

issue

3

eissn

0360-4012

issn

1097-4547

pii

10.1002/(SICI)1097-4547(19990201)55:3<293::AID-JNR

journal_volume

55

pub_type

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