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Science 18 December 1987:
Vol. 238. no. 4834, pp. 1726 - 1728
DOI: 10.1126/science.3686012
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Articles

Science, Vol 238, Issue 4834, 1726-1728
Copyright © 1987 by American Association for the Advancement of Science

articles

Protein kinase C contains a pseudosubstrate prototope in its regulatory domain

C House and BE Kemp

Department of Medicine, University of Melbourne, Repatriation General Hospital, West Heidelberg, Victoria, Australia.

The regulatory domain of protein kinase C contains an amino acid sequence between residues 19 and 36 that resembles a substrate phosphorylation site in its distribution of basic residue recognition determinants. The corresponding synthetic peptide (Arg19-Phe-Ala-Arg-Lys-Gly-Ala25-Leu-Arg-Gln-Lys-Asn-Val-His -Glu-Val-Lys-Asn36) acts as a potent substrate antagonist with an inhibitory constant of 147 +/- 9 nM. It is a specific inhibitor of protein kinase C and inhibits both autophosphorylation and protein substrate phosphorylation. Substitution of Ala25 with serine transforms the pseudosubstrate into a potent substrate. These results demonstrate that the conserved region of the regulatory domain (residues 19 to 36) of protein kinase C has the secondary structural features of a pseudosubstrate and may be responsible for maintaining the enzyme in the inactive form in the absence of allosteric activators such as phospholipids.


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   Abstract »    Full Text »    PDF »
Calcium/calmodulin-dependent protein kinase II controls alpha5beta1 integrin-mediated inside-out signaling.
D Bouvard, A Molla, and M. Block (1998)
J. Cell Sci. 111, 657-665
   Abstract »    PDF »
Anchoring proteins for protein kinase C: a means for isozyme selectivity.
D. Mochly-rosen and A. S. Gordon (1998)
FASEB J 12, 35-42
   Abstract »    Full Text »
Nucleolin Is a Protein Kinase C-zeta Substrate. CONNECTION BETWEEN CELL SURFACE SIGNALING AND NUCLEUS IN PC12 CELLS.
G. Zhou, M. L. Seibenhener, and M. W. Wooten (1997)
J. Biol. Chem. 272, 31130-31137
   Abstract »    Full Text »    PDF »
Interaction of a Receptor Tyrosine Kinase, EGF-R, with Caveolins. CAVEOLIN BINDING NEGATIVELY REGULATES TYROSINE AND SERINE/THREONINE KINASE ACTIVITIES.
J. Couet, M. Sargiacomo, and M. P. Lisanti (1997)
J. Biol. Chem. 272, 30429-30438
   Abstract »    Full Text »    PDF »
20-Hydroxyeicosatetraenoic Acid-induced Vasoconstriction and Inhibition of Potassium Current in Cerebral Vascular Smooth Muscle Is Dependent on Activation of Protein Kinase C.
A. Lange, D. Gebremedhin, J. Narayanan, and D. Harder (1997)
J. Biol. Chem. 272, 27345-27352
   Abstract »    Full Text »    PDF »
Monochloramine Inhibits Phorbol Ester-inducible Neutrophil Respiratory Burst Activation and T Cell Interleukin-2 Receptor Expression by Inhibiting Inducible Protein Kinase C Activity.
T. Ogino, H. Kobuchi, C. K. Sen, S. Roy, L. Packer, and J. J. Maguire (1997)
J. Biol. Chem. 272, 26247-26252
   Abstract »    Full Text »    PDF »
Dopaminergic Modulation of Sodium Current in Hippocampal Neurons via cAMP-Dependent Phosphorylation of Specific Sites in the Sodium Channel alpha  Subunit.
A. R. Cantrell, R. D. Smith, A. L. Goldin, T. Scheuer, and W. A. Catterall (1997)
J. Neurosci. 17, 7330-7338
   Abstract »    Full Text »    PDF »
Role of protein kinase C in calcium sensitization during muscarinic stimulation in airway smooth muscle.
D. H. Bremerich, D. O. Warner, R. R. Lorenz, R. Shumway, and K. A. Jones (1997)
Am J Physiol Lung Cell Mol Physiol 273, L775-L781
   Abstract »    Full Text »    PDF »
Regulation of Mouse Skeletal Muscle L-Type Ca2+ Channel by Activation of the Insulin-Like Growth Factor-1 Receptor.
O. Delbono, M. Renganathan, and M. L. Messi (1997)
J. Neurosci. 17, 6918-6928
   Abstract »    Full Text »    PDF »
Regulation of Protein Kinase Cµ by Basic Peptides and Heparin. PUTATIVE ROLE OF AN ACIDIC DOMAIN IN THE ACTIVATION OF THE KINASE.
M. Gschwendt, F.-J. Johannes, W. Kittstein, and F. Marks (1997)
J. Biol. Chem. 272, 20742-20746
   Abstract »    Full Text »    PDF »
Binding of Polyamines to an Autonomous Domain of the Regulatory Subunit of Protein Kinase CK2 Induces a Conformational Change in the Holoenzyme. A PROPOSED ROLE FOR THE KINASE STIMULATION.
D. Leroy, J.-K. Heriche, O. Filhol, E. M. Chambaz, and C. Cochet (1997)
J. Biol. Chem. 272, 20820-20827
   Abstract »    Full Text »    PDF »
Phosphorylation of Sendai Virus Phosphoprotein by Cellular Protein Kinase C zeta.
C. C. Huntley, B. P. De, and A. K. Banerjee (1997)
J. Biol. Chem. 272, 16578-16584
   Abstract »    Full Text »    PDF »
Ca2+ as a Mediator of Ischemic Preconditioning.
H. Miyawaki and M. Ashraf (1997)
Circ. Res. 80, 790-799
   Abstract »    Full Text »
C2 Region–Derived Peptides of ß-Protein Kinase C Regulate Cardiac Ca2+ Channels.
Z.-H. Zhang, J. A. Johnson, L. Chen, N. El-Sherif, D. Mochly-Rosen, and M. Boutjdir (1997)
Circ. Res. 80, 720-729
   Abstract »    Full Text »
Isolation and Characterization of a Structural Homologue of Human PRK2 from Rat Liver. DISTINGUISHING SUBSTRATE AND LIPID ACTIVATOR SPECIFICITIES.
W. Yu, J. Liu, N. A. Morrice, and R. E.H. Wettenhall (1997)
J. Biol. Chem. 272, 10030-10034
   Abstract »    Full Text »    PDF »
Structure and Expression of the Caenorhabditis elegans Protein Kinase C2 Gene. ORIGINS AND REGULATED EXPRESSION OF A FAMILY OF Ca2+-ACTIVATED PROTEIN KINASE C ISOFORMS.
A. Islas-Trejo, M. Land, I. Tcherepanova, J. H. Freedman, and C. S. Rubin (1997)
J. Biol. Chem. 272, 6629-6640
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Different Protein Kinase C Isozymes Mediate Lower Esophageal Sphincter Tone and Phasic Contraction of Esophageal Circular Smooth Muscle.
U. D. Sohn, D. Zoukhri, D. Dartt, C. Sergheraert, K. M. Harnett, J. Behar, and P. Biancani (1997)
Mol. Pharmacol. 51, 462-470
   Abstract »    Full Text »    PDF »
Modulation of Protein Kinase C Activity in Plasmodium falciparum - Infected Erythrocytes.
B. S. Hall, O. O. Daramola, G. Barden, and G. A.T. Targett (1997)
Blood 89, 1770-1778
   Abstract »    Full Text »    PDF »
Autophosphorylation of Dictyostelium Myosin II Heavy Chain-specific Protein Kinase C Is Required for Its Activation and Membrane Dissociation.
A. Dembinsky, H. Rubin, and S. Ravid (1997)
J. Biol. Chem. 272, 828-834
   Abstract »    Full Text »    PDF »


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