| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J Biol Chem, Vol. 273, Issue 28, 17544-17552, July 10, 1998
From the Department of Chemistry, University of Illinois, Chicago,
Illinois 60607-7061
The C2 domains of conventional protein kinase C
(PKC) have been implicated in their
Ca2+-dependent membrane binding. The C2
domain of PKC-
contains several Ca2+ ligands that bind
multiple Ca2+ ions and other putative membrane binding
residues. To understand the roles of individual Ca2+
ligands and protein-bound Ca2+ ions in the membrane binding
and activation of PKC-, we mutated five putative Ca2+
ligands (D187N, D193N, D246N, D248N, and D254N) and measured the
effects of mutations on vesicle binding, enzyme activity, and monolayer
penetration of PKC-. Altered properties of these mutants indicate
that individual Ca2+ ions and their ligands have different
roles in the membrane binding and activation of PKC-. The binding of
Ca2+ to Asp187, Asp193, and
Asp246 of PKC- is important for the initial binding of
protein to membrane surfaces. On the other hand, the binding of another
Ca2+ to Asp187, Asp246,
Asp248, and Asp254 induces the conformational
change of PKC-, which in turn triggers its membrane penetration and
activation. Among these Ca2+ ligands, Asp246
was shown to be most essential for both membrane binding and activation
of PKC-, presumably due to its coordination to multiple Ca2+ ions. Furthermore, to identify the residues in the C2
domain that are involved in membrane binding of PKC-, we mutated
four putative membrane binding residues (Trp245,
Trp247, Arg249, and Arg252).
Membrane binding and enzymatic properties of two double-site mutants
(W245A/W247A and R249A/R252A) indicate that Arg249 and
Arg252 are involved in electrostatic interactions of
PKC- with anionic membranes, whereas Trp245 and
Trp247 participate in its penetration into membranes and
resulting hydrophobic interactions. Taken together, these studies
provide the first experimental evidence for the role of C2 domain of
conventional PKC as a membrane docking unit as well as a module that
triggers conformational changes to activate the protein.
This article has been cited by other articles:
|
|
 |
|
  H. R. Melowic, R. V. Stahelin, N. R. Blatner, W. Tian, K. Hayashi, A. Altman, and W. Cho Mechanism of Diacylglycerol-induced Membrane Targeting and Activation of Protein Kinase C{theta} J. Biol. Chem., July 20, 2007; 282(29): 21467 - 21476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. T. Wijewickrama, A. Albanese, Y. J. Kim, Y. S. Oh, P. S. Murray, R. Takayanagi, T. Tobe, S. Masuda, M. Murakami, I. Kudo, et al. Unique Membrane Interaction Mode of Group IIF Phospholipase A2 J. Biol. Chem., October 27, 2006; 281(43): 32741 - 32754. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Reither, M. Schaefer, and P. Lipp PKC{alpha}: a versatile key for decoding the cellular calcium toolkit J. Cell Biol., August 14, 2006; 174(4): 521 - 533. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Evans, D. Murray, C. C. Leslie, and J. J. Falke Specific Translocation of Protein Kinase C{alpha} to the Plasma Membrane Requires Both Ca2+ and PIP2 Recognition by Its C2 Domain Mol. Biol. Cell, January 1, 2006; 17(1): 56 - 66. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. V. Stahelin, J. H. Hwang, J.-H. Kim, Z.-Y. Park, K. R. Johnson, L. M. Obeid, and W. Cho The Mechanism of Membrane Targeting of Human Sphingosine Kinase 1 J. Biol. Chem., December 30, 2005; 280(52): 43030 - 43038. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. V. Stahelin, J. Wang, N. R. Blatner, J. D. Rafter, D. Murray, and W. Cho The Origin of C1A-C2 Interdomain Interactions in Protein Kinase C{alpha} J. Biol. Chem., October 28, 2005; 280(43): 36452 - 36463. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. V. Stahelin, M. A. Digman, M. Medkova, B. Ananthanarayanan, H. R. Melowic, J. D. Rafter, and W. Cho Diacylglycerol-induced Membrane Targeting and Activation of Protein Kinase C{epsilon}: MECHANISTIC DIFFERENCES BETWEEN PROTEIN KINASES C{delta} AND C{epsilon} J. Biol. Chem., May 20, 2005; 280(20): 19784 - 19793. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. V. Stahelin, M. A. Digman, M. Medkova, B. Ananthanarayanan, J. D. Rafter, H. R. Melowic, and W. Cho Mechanism of Diacylglycerol-induced Membrane Targeting and Activation of Protein Kinase C{delta} J. Biol. Chem., July 9, 2004; 279(28): 29501 - 29512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Jose Lopez-Andreo, J. C. Gomez-Fernandez, and S. Corbalan-Garcia The Simultaneous Production of Phosphatidic Acid and Diacylglycerol Is Essential for the Translocation of Protein Kinase C{epsilon} to the Plasma Membrane in RBL-2H3 Cells Mol. Biol. Cell, December 1, 2003; 14(12): 4885 - 4895. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Trushin, K. N. Pennington, E. M. Carmona, S. Asin, D. N. Savoy, D. D. Billadeau, and C. V. Paya Protein Kinase C{alpha} (PKC{alpha}) Acts Upstream of PKC{theta} To Activate I{kappa}B Kinase and NF-{kappa}B in T Lymphocytes Mol. Cell. Biol., October 1, 2003; 23(19): 7068 - 7081. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. V. Stahelin, F. Long, B. J. Peter, D. Murray, P. De Camilli, H. T. McMahon, and W. Cho Contrasting Membrane Interaction Mechanisms of AP180 N-terminal Homology (ANTH) and Epsin N-terminal Homology (ENTH) Domains J. Biol. Chem., August 1, 2003; 278(31): 28993 - 28999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. V. Stahelin, J. D. Rafter, S. Das, and W. Cho The Molecular Basis of Differential Subcellular Localization of C2 Domains of Protein Kinase C-alpha and Group IVa Cytosolic Phospholipase A2 J. Biol. Chem., March 28, 2003; 278(14): 12452 - 12460. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Bolsover, J. C. Gomez-Fernandez, and S. Corbalan-Garcia Role of the Ca2+/Phosphatidylserine Binding Region of the C2 Domain in the Translocation of Protein Kinase Calpha to the Plasma Membrane J. Biol. Chem., March 14, 2003; 278(12): 10282 - 10290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Corbalan-Garcia, J. Garcia-Garcia, J. A. Rodriguez-Alfaro, and J. C. Gomez-Fernandez A New Phosphatidylinositol 4,5-Bisphosphate-binding Site Located in the C2 Domain of Protein Kinase Calpha J. Biol. Chem., February 7, 2003; 278(7): 4972 - 4980. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Baillie, E. Huston, G. Scotland, M. Hodgkin, I. Gall, A. H. Peden, C. MacKenzie, E. S. Houslay, R. Currie, T. R. Pettitt, et al. TAPAS-1, a Novel Microdomain within the Unique N-terminal Region of the PDE4A1 cAMP-specific Phosphodiesterase That Allows Rapid, Ca2+-triggered Membrane Association with Selectivity for Interaction with Phosphatidic Acid J. Biol. Chem., July 26, 2002; 277(31): 28298 - 28309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Banci, G. Cavallaro, V. Kheifets, and D. Mochly-Rosen Molecular Dynamics Characterization of the C2 Domain of Protein Kinase Cbeta J. Biol. Chem., April 5, 2002; 277(15): 12988 - 12997. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Han, J. H. Kim, B. D. Lee, S. D. Lee, Y. Kim, Y. W. Jung, S. Lee, W. Cho, M. Ohba, T. Kuroki, et al. Phosphorylation-dependent Regulation of Phospholipase D2 by Protein Kinase Cdelta in Rat Pheochromocytoma PC12 Cells J. Biol. Chem., March 1, 2002; 277(10): 8290 - 8297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Plant, F. Lafont, S. Lecat, P. Verkade, K. Simons, and D. Rotin Apical Membrane Targeting of Nedd4 Is Mediated by an Association of Its C2 Domain with Annexin XIIIb J. Cell Biol., June 26, 2000; 149(7): 1473 - 1484. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Feng, K. P. Becker, S. D. Stribling, K. G. Peters, and Y. A. Hannun Regulation of Receptor-mediated Protein Kinase C Membrane Trafficking by Autophosphorylation J. Biol. Chem., May 26, 2000; 275(22): 17024 - 17034. [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]
|
|
|
|
|
|
M. Medkova and W. Cho Interplay of C1 and C2 Domains of Protein Kinase C-alpha in Its Membrane Binding and Activation J. Biol. Chem., July 9, 1999; 274(28): 19852 - 19861. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Gijon, D. M. Spencer, A. L. Kaiser, and C. C. Leslie Role of Phosphorylation Sites and the C2 Domain in Regulation of Cytosolic Phospholipase A2 J. Cell Biol., June 14, 1999; 145(6): 1219 - 1232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Perisic, H. F. Paterson, G. Mosedale, S. Lara-Gonzalez, and R. L. Williams Mapping the Phospholipid-binding Surface and Translocation Determinants of the C2 Domain from Cytosolic Phospholipase A2 J. Biol. Chem., May 21, 1999; 274(21): 14979 - 14987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Bittova, M. Sumandea, and W. Cho A Structure-Function Study of the C2 Domain of Cytosolic Phospholipase A2. IDENTIFICATION OF ESSENTIAL CALCIUM LIGANDS AND HYDROPHOBIC MEMBRANE BINDING RESIDUES J. Biol. Chem., April 2, 1999; 274(14): 9665 - 9672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Pepio and W. S. Sossin Membrane Translocation of Novel Protein Kinase Cs Is Regulated by Phosphorylation of the C2 Domain J. Biol. Chem., February 2, 2001; 276(6): 3846 - 3855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Bittova, R. V. Stahelin, and W. Cho Roles of Ionic Residues of the C1 Domain in Protein Kinase C-alpha Activation and the Origin of Phosphatidylserine Specificity J. Biol. Chem., February 2, 2001; 276(6): 4218 - 4226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Ananthanarayanan, S. Das, S. G. Rhee, D. Murray, and W. Cho Membrane Targeting of C2 Domains of Phospholipase C-delta Isoforms J. Biol. Chem., January 25, 2002; 277(5): 3568 - 3575. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Radominska-Pandya, G. Chen, P. J. Czernik, J. M. Little, V. M. Samokyszyn, C. A. Carter, and G.{m. d.}y. Nowak Direct Interaction of All-trans-retinoic Acid with Protein Kinase C (PKC). IMPLICATIONS FOR PKC SIGNALING AND CANCER THERAPY J. Biol. Chem., July 14, 2000; 275(29): 22324 - 22330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Cho Membrane Targeting by C1 and C2 Domains J. Biol. Chem., August 24, 2001; 276(35): 32407 - 32410. [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Garcia, C. E. Forde, and H. A. Godwin Calcium triggers an intramolecular association of the C2 domains in synaptotagmin PNAS, May 23, 2000; 97(11): 5883 - 5888. [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 |
