| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Journal of Lipid Research, Vol. 45, 496-506, March 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology
* Department of Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, SC 29425
Research and Development, Ralph H. Johnson Veterans Administration Medical Center, Charleston, SC 29401
1 To whom correspondence should be addressed. e-mail: hannun{at}musc.edu
The protein phosphatases1 (PP1) and 2A (PP2A) serve as ceramide-activated protein phosphatases (CAPP). In this study, the structural requirements for interaction between ceramide and CAPP were determined. D-erythro-C6 ceramide activated the catalytic subunit of PP2A (PP2Ac) approximately 3-fold in a stereospecific manner. In contrast, saturation of the 4-5 double bond, producing D-erythro-dihydro C6 ceramide, inhibited PP2Ac (IC50 = 8.5 µM). Furthermore, phyto C6 ceramide, D-erythro-dehydro C6 ceramide, and D-erythro-cis-C6 ceramide had no effect on PP2Ac activity. Modification of the sphingoid chain also abolished the ability of ceramide to activate PP2Ac. Further studies demonstrated the requirement for the amide group, the primary hydroxyl group, and the secondary hydroxyl group of the sphingoid backbone for activation of PP2Ac through the synthesis and evaluation of D-erythro-urea C6 ceramide, L-erythro-urea C6 ceramide, D-erythro-N-methyl C6 ceramide, D-erythro-1-O-methyl C6 ceramide, D-erythro-3-O-methyl C6 ceramide, and (2S) 3-keto C6 ceramide. None of these compounds induced significant activation of PP2Ac. Liposome binding studies were also conducted using analogs of D-erythro-C C6 ceramide, and the results showed that the ability of ceramide analogs to influence CAPP (activation or inhibition) was associated with the ability of the analogs to bind to CAPP.
This study demonstrates strict structural requirements for interaction of ceramide with CAPP, and disclose ceramide as a very specific regulator of CAPP. The studies also begin to define features that transform ceramide analogs into inhibitors of CAPP.
Abbreviations: PP1, protein phosphatase-1; PP2A, protein phosphatase-2A
Supplementary key words protein phosphatase-2A • protein phosphatase-1 • ceramide-activated protein phosphatase
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. A. Novgorodov, T. I. Gudz, and L. M. Obeid Long-chain Ceramide Is a Potent Inhibitor of the Mitochondrial Permeability Transition Pore J. Biol. Chem., September 5, 2008; 283(36): 24707 - 24717. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. H. Zeidan, R. W. Jenkins, and Y. A. Hannun Remodeling of cellular cytoskeleton by the acid sphingomyelinase/ceramide pathway J. Cell Biol., April 21, 2008; 181(2): 335 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kitatani, J. Idkowiak-Baldys, and Y. A. Hannun Mechanism of Inhibition of Sequestration of Protein Kinase C {alpha}/betaII by Ceramide: ROLES OF CERAMIDE-ACTIVATED PROTEIN PHOSPHATASES AND PHOSPHORYLATION/DEPHOSPHORYLATION OF PROTEIN KINASE C {alpha}/betaII ON THREONINE 638/641 J. Biol. Chem., July 13, 2007; 282(28): 20647 - 20656. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Eyster The membrane and lipids as integral participants in signal transduction: lipid signal transduction for the non-lipid biochemist Advan Physiol Educ, March 1, 2007; 31(1): 5 - 16. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ghosh, N. Patel, K. Jiang, J. E. Watson, J. Cheng, C. E. Chalfant, and D. R. Cooper Ceramide-Activated Protein Phosphatase Involvement in Insulin Resistance via Akt, Serine/Arginine-Rich Protein 40, and Ribonucleic Acid Splicing in L6 Skeletal Muscle Cells Endocrinology, March 1, 2007; 148(3): 1359 - 1366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Jin, E. K. Blue, and P. J. Gallagher Control of Death-associated Protein Kinase (DAPK) Activity by Phosphorylation and Proteasomal Degradation J. Biol. Chem., December 22, 2006; 281(51): 39033 - 39040. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. Ghering and W. S. Davidson Ceramide structural features required to stimulate ABCA1-mediated cholesterol efflux to apolipoprotein A-I J. Lipid Res., December 1, 2006; 47(12): 2781 - 2788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Wijesinghe, A. Massiello, P. Subramanian, Z. Szulc, A. Bielawska, and C. E. Chalfant Substrate specificity of human ceramide kinase J. Lipid Res., December 1, 2005; 46(12): 2706 - 2716. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Wang, J. Silva, K. Krishnamurthy, E. Tran, B. G. Condie, and E. Bieberich Direct Binding to Ceramide Activates Protein Kinase C{zeta} before the Formation of a Pro-apoptotic Complex with PAR-4 in Differentiating Stem Cells J. Biol. Chem., July 15, 2005; 280(28): 26415 - 26424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. L. Brockman, M. M. Momsen, R. E. Brown, L. He, J. Chun, H.-S. Byun, and R. Bittman The 4,5-Double Bond of Ceramide Regulates Its Dipole Potential, Elastic Properties, and Packing Behavior Biophys. J., September 1, 2004; 87(3): 1722 - 1731. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |
