| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J Biol Chem, Vol. 273, Issue 36, 23160-23168, September 4, 1998
Activity by Phorbol Esters, Diacylglycerols, and Bryostatin-1
From the Department of Pathology and Cell Biology, Thomas Jefferson
University, Philadelphia, Pennsylvania 19107
The activity of membrane-associated protein
kinase C (PKC) has previously been shown to be regulated by two
discrete high and low affinity binding regions for diacylglycerols and
phorbol esters (Slater, S. J., Ho, C., Kelly, M. B., Larkin,
J. D., Taddeo, F. J., Yeager, M. D., and Stubbs, C. D. (1996) J. Biol. Chem. 271, 4627-4631). PKC is also
known to interact with both cytoskeletal and nuclear proteins; however,
less is known concerning the mode of activation of this non-membrane
form of PKC. By using the fluorescent phorbol ester, sapintoxin D
(SAPD), PKC
, alone, was found to possess both low and high affinity
phorbol ester-binding sites, showing that interaction with these sites
does not require association with the membrane. Importantly, a fusion
protein containing the isolated C1A/C1B (C1) domain of PKC also
bound SAPD with low and high affinity, indicating that the sites may be
confined to this domain rather than residing elsewhere on the enzyme
molecule. Both high and low affinity interactions with native PKC
were enhanced by protamine sulfate, which activates the enzyme without requiring Ca2+ or membrane lipids. However, this
"non-membrane" PKC activity was inhibited by the phorbol ester
4
-12-O-tetradecanoylphorbol-13-acetate (TPA) and also by
the fluorescent analog, SAPD, opposite to its effect on
membrane-associated PKC. Bryostatin-1 and the soluble diacylglycerol, 1-oleoyl-2-acetylglycerol, both potent activators of
membrane-associated PKC, also competed for both low and high affinity
SAPD binding and inhibited protamine sulfate-induced activity.
Furthermore, the inactive phorbol ester analog 4-TPA (4-12-O-tetradecanoylphorbol-13-acetate) also inhibited
non-membrane-associated PKC. In keeping with these observations,
although TPA could displace high affinity SAPD binding from both forms
of the enzyme, 4-TPA was only effective at displacing high affinity
SAPD binding from non-membrane-associated PKC. 4-TPA also displaced
SAPD from the isolated C1 domain. These results show that although high
and low affinity phorbol ester-binding sites are found on
non-membrane-associated PKC, the phorbol ester binding properties
change significantly upon association with membranes.
This article has been cited by other articles:
|
|
 |
|
  J. Das, X. Zhou, and K. W. Miller Identification of an alcohol binding site in the first cysteine-rich domain of protein kinase C {delta}. Protein Sci., September 1, 2006; 15(9): 2107 - 2119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Cheeseman, T. Ueyama, T. M. Michaud, K. Kashiwagi, D. Wang, L. A. Flax, Y. Shirai, D. J. Loegering, N. Saito, and M. R. Lennartz Targeting of Protein Kinase C-{epsilon} during Fc{gamma} Receptor-dependent Phagocytosis Requires the {epsilon}C1B Domain and Phospholipase C-{gamma}1 Mol. Biol. Cell, February 1, 2006; 17(2): 799 - 813. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Das, G. H. Addona, W. S. Sandberg, S. S. Husain, T. Stehle, and K. W. Miller Identification of a General Anesthetic Binding Site in the Diacylglycerol-binding Domain of Protein Kinase C{delta} J. Biol. Chem., September 3, 2004; 279(36): 37964 - 37972. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Slater, J. L. Seiz, A. C. Cook, C. J. Buzas, S. A. Malinowski, J. L. Kershner, B. A. Stagliano, and C. D. Stubbs Regulation of PKCalpha Activity by C1-C2 Domain Interactions J. Biol. Chem., May 3, 2002; 277(18): 15277 - 15285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. NEUZIL, T. WEBER, A. SCHRODER, M. LU, G. OSTERMANN, N. GELLERT, G. C. MAYNE, B. OLEJNICKA, A. NEGRE-SALVAYRE, M. STICHA, et al. Induction of cancer cell apoptosis by {alpha}-tocopheryl succinate: molecular pathways and structural requirements FASEB J, February 1, 2001; 15(2): 403 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. RON and M. G. KAZANIETZ New insights into the regulation of protein kinase C and novel phorbol ester receptors FASEB J, October 1, 1999; 13(13): 1658 - 1676. [Abstract] [Full Text]
|
|
|
|
|
|
Q. J. Wang, T.-W. Fang, K. Nacro, V. E. Marquez, S. Wang, and P. M. Blumberg Role of Hydrophobic Residues in the C1b Domain of Protein Kinase C delta on Ligand and Phospholipid Interactions J. Biol. Chem., May 25, 2001; 276(22): 19580 - 19587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Caloca, H. Wang, A. Delemos, S. Wang, and M. G. Kazanietz Phorbol Esters and Related Analogs Regulate the Subcellular Localization of beta 2-Chimaerin, a Non-protein Kinase C Phorbol Ester Receptor J. Biol. Chem., May 18, 2001; 276(21): 18303 - 18312. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
