Differential effects of ceramides upon adenylyl cyclase subtypes

FEBS Letters

Pfeuffer, Thomas¹  Bösel, Angela¹ 

[1] Department of Physiological Chemistry II, Heinrich-Heine-University, P.O. Box 101007, D-40001 Düsseldorf, Germany

关键词: Adenylyl cyclase type II;    Ceramide;    Phorbolester;    Okadaic acid;   

DOI  :  10.1016/S0014-5793(97)01620-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Ceramides are reported to stimulate different effector systems, among them atypical protein kinases C (PKCs). When HEK 293 cells, stably expressing adenylyl cyclase type II (AC II), were treated with various ceramide derivatives, adenylyl cyclase activity was enhanced 8–15-fold. The stimulation by the most potent analog, C₁₈/C₂₄ ceramide, was comparable to that by the phorbolester TPA. The stimulatory effect of ceramide was not restricted to AC II, although the type I and type V enzymes were affected less dramatically. Unexpectedly, the dihydro derivatives of ceramides, generally serving as non-activating controls, exhibited only slightly lower stimulation than ceramides, whereas short-chain ceramides (e.g. C₂) were without effect. The action of ceramides was at least partially inhibited by okadaic acid, suggesting involvement of a phosphatase. Furthermore, ceramides and TPA operated synergistically. While the PKC inhibitor staurosporine counteracted the action of phorbolesters, it significantly (2.5×) enhanced the effect of ceramides.

【 授权许可】

Unknown