PDBsum entry 1ptq

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protein metals links
Phosphotransferase PDB id
Protein chain
50 a.a. *
_ZN ×2
* Residue conservation analysis
PDB id:
Name: Phosphotransferase
Title: Protein kinasE C delta cys2 domain
Structure: Protein kinasE C delta type. Chain: a. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.95Å     R-factor:   0.196    
Authors: G.Zhang,J.H.Hurley
Key ref: G.Zhang et al. (1995). Crystal structure of the cys2 activator-binding domain of protein kinase C delta in complex with phorbol ester. Cell, 81, 917-924. PubMed id: 7781068 DOI: 10.1016/0092-8674(95)90011-X
11-May-95     Release date:   31-Jul-95    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P28867  (KPCD_MOUSE) -  Protein kinase C delta type
674 a.a.
50 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: E.C.  - Non-specific protein-tyrosine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
+ [protein]-L-tyrosine
+ [protein]-L-tyrosine phosphate
   Enzyme class 3: E.C.  - Protein kinase C.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
+ protein
+ phosphoprotein
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     intracellular signal transduction   1 term 


DOI no: 10.1016/0092-8674(95)90011-X Cell 81:917-924 (1995)
PubMed id: 7781068  
Crystal structure of the cys2 activator-binding domain of protein kinase C delta in complex with phorbol ester.
G.Zhang, M.G.Kazanietz, P.M.Blumberg, J.H.Hurley.
Protein kinase Cs (PKCs) are a ubiquitous family of regulatory enzymes that associate with membranes and are activated by diacylglycerol or tumor-promoting agonists such as phorbol esters. The structure of the second activator-binding domain of PKC delta has been determined in complex with phorbol 13-acetate, which binds in a groove between two pulled-apart beta strands at the tip of the domain. The C3, C4, and C20 phorbol oxygens form hydrogen bonds with main-chain groups whose orientation is controlled by a set of highly conserved residues. Phorbol binding caps the groove and forms a contiguous hydrophobic surface covering one-third of the domain, explaining how the activator promotes insertion of PKC into membranes.

Literature references that cite this PDB file's key reference

  PubMed id Reference
23235882 S.Lekomtsev, K.C.Su, V.E.Pye, K.Blight, S.Sundaramoorthy, T.Takaki, L.M.Collinson, P.Cherepanov, N.Divecha, and M.Petronczki (2012).
Centralspindlin links the mitotic spindle to the plasma membrane during cytokinesis.
  Nature, 492, 276-279.
PDB code: 4b6d
21388717 D.Colombo, C.Tringali, L.Franchini, F.Cirillo, and B.Venerando (2011).
Glycoglycerolipid analogues inhibit PKC translocation to the plasma membrane and downstream signaling pathways in PMA-treated fibroblasts and human glioblastoma cells, U87MG.
  Eur J Med Chem, 46, 1827-1834.  
21067413 F.Zhao, M.Ilbert, R.Varadan, C.M.Cremers, B.Hoyos, R.Acin-Perez, V.Vinogradov, D.Cowburn, U.Jakob, and U.Hammerling (2011).
Are zinc-finger domains of protein kinase C dynamic structures that unfold by lipid or redox activation?
  Antioxid Redox Signal, 14, 757-766.  
21419781 M.D.Stewart, B.Morgan, F.Massi, and T.I.Igumenova (2011).
Probing the determinants of diacylglycerol binding affinity in the C1B domain of protein kinase Cα.
  J Mol Biol, 408, 949-970.  
21215369 T.A.Leonard, B.Różycki, L.F.Saidi, G.Hummer, and J.H.Hurley (2011).
Crystal structure and allosteric activation of protein kinase C βII.
  Cell, 144, 55-66.
PDB code: 3pfq
19934406 A.C.Newton (2010).
Protein kinase C: poised to signal.
  Am J Physiol Endocrinol Metab, 298, E395-E402.  
20100661 A.Majhi, G.M.Rahman, S.Panchal, and J.Das (2010).
Binding of curcumin and its long chain derivatives to the activator binding domain of novel protein kinase C.
  Bioorg Med Chem, 18, 1591-1598.  
20164256 H.Wang, and M.G.Kazanietz (2010).
p23/Tmp21 differentially targets the Rac-GAP beta2-chimaerin and protein kinase C via their C1 domains.
  Mol Biol Cell, 21, 1398-1408.  
20018888 K.Deng, Y.Gao, Z.Cao, E.I.Graziani, A.Wood, P.Doherty, and F.S.Walsh (2010).
Overcoming amino-Nogo-induced inhibition of cell spreading and neurite outgrowth by 12-O-tetradecanoylphorbol-13-acetate-type tumor promoters.
  J Biol Chem, 285, 6425-6433.  
20354984 K.J.Hale, and S.Manaviazar (2010).
New approaches to the total synthesis of the bryostatin antitumor macrolides.
  Chem Asian J, 5, 704-754.  
19636513 S.A.Mason, S.J.Cozzi, C.J.Pierce, S.J.Pavey, P.G.Parsons, and G.M.Boyle (2010).
The induction of senescence-like growth arrest by protein kinase C-activating diterpene esters in solid tumor cells.
  Invest New Drugs, 28, 575-586.  
19218317 A.J.King, W.He, J.A.Cuevas, M.Freudenberger, D.Ramiaramanana, and I.A.Graham (2009).
Potential of Jatropha curcas as a source of renewable oil and animal feed.
  J Exp Bot, 60, 2897-2905.  
19489582 B.J.Morgan, S.Dey, S.W.Johnson, and M.C.Kozlowski (2009).
Design, synthesis, and investigation of protein kinase C inhibitors: total syntheses of (+)-calphostin D, (+)-phleichrome, cercosporin, and new photoactive perylenequinones.
  J Am Chem Soc, 131, 9413-9425.  
19432558 J.Das, S.Pany, G.M.Rahman, and S.J.Slater (2009).
PKC epsilon has an alcohol-binding site in its second cysteine-rich regulatory domain.
  Biochem J, 421, 405-413.  
19131951 L.Bordoli, F.Kiefer, K.Arnold, P.Benkert, J.Battey, and T.Schwede (2009).
Protein structure homology modeling using SWISS-MODEL workspace.
  Nat Protoc, 4, 1.  
19672879 N.Ohashi, W.Nomura, M.Kato, T.Narumi, N.E.Lewin, P.M.Blumberg, and H.Tamamura (2009).
Synthesis of protein kinase Cdelta C1b domain by native chemical ligation methodology and characterization of its folding and ligand binding.
  J Pept Sci, 15, 642-646.  
19008549 R.V.Stahelin (2009).
Lipid binding domains: more than simple lipid effectors.
  J Lipid Res, 50, S299-S304.  
19233655 T.J.Nelson, and D.L.Alkon (2009).
Neuroprotective versus tumorigenic protein kinase C activators.
  Trends Biochem Sci, 34, 136-145.  
19710537 X.Yin, M.Zafrullah, H.Lee, A.Haimovitz-Friedman, Z.Fuks, and R.Kolesnick (2009).
A ceramide-binding C1 domain mediates kinase suppressor of ras membrane translocation.
  Cell Physiol Biochem, 24, 219-230.  
19001377 Y.Pu, S.H.Garfield, N.Kedei, and P.M.Blumberg (2009).
Characterization of the differential roles of the twin C1a and C1b domains of protein kinase C-delta.
  J Biol Chem, 284, 1302-1312.  
18505819 C.A.Farah, I.Nagakura, D.Weatherill, X.Fan, and W.S.Sossin (2008).
Physiological role for phosphatidic acid in the translocation of the novel protein kinase C Apl II in Aplysia neurons.
  Mol Cell Biol, 28, 4719-4733.  
18698758 D.Duan, D.M.Sigano, J.A.Kelley, C.C.Lai, N.E.Lewin, N.Kedei, M.L.Peach, J.Lee, T.P.Abeyweera, S.A.Rotenberg, H.Kim, Y.H.Kim, S.El Kazzouli, J.U.Chung, H.A.Young, M.R.Young, A.Baker, N.H.Colburn, A.Haimovitz-Friedman, J.P.Truman, D.A.Parrish, J.R.Deschamps, N.A.Perry, R.J.Surawski, P.M.Blumberg, and V.E.Marquez (2008).
Conformationally constrained analogues of diacylglycerol. 29. Cells sort diacylglycerol-lactone chemical zip codes to produce diverse and selective biological activities.
  J Med Chem, 51, 5198-5220.  
18187412 D.R.Dries, and A.C.Newton (2008).
Kinetic analysis of the interaction of the C1 domain of protein kinase C with lipid membranes by stopped-flow spectroscopy.
  J Biol Chem, 283, 7885-7893.  
18391402 J.Agniswamy, M.G.Joyce, C.H.Hammer, and P.D.Sun (2008).
Towards a rational approach for heavy-atom derivative screening in protein crystallography.
  Acta Crystallogr D Biol Crystallogr, 64, 354-367.  
18511940 J.Rapley, V.L.Tybulewicz, and K.Rittinger (2008).
Crucial structural role for the PH and C1 domains of the Vav1 exchange factor.
  EMBO Rep, 9, 655-661.
PDB code: 2vrw
18216767 M.A.Lemmon (2008).
Membrane recognition by phospholipid-binding domains.
  Nat Rev Mol Cell Biol, 9, 99.  
18707088 S.El Kazzouli, N.E.Lewin, P.M.Blumberg, and V.E.Marquez (2008).
Conformationally constrained analogues of diacylglycerol. 30. An investigation of diacylglycerol-lactones containing heteroaryl groups reveals compounds with high selectivity for Ras guanyl nucleotide-releasing proteins.
  J Med Chem, 51, 5371-5386.  
  18923184 S.F.Steinberg (2008).
Structural basis of protein kinase C isoform function.
  Physiol Rev, 88, 1341-1378.  
18263588 S.H.Choi, G.Czifra, N.Kedei, N.E.Lewin, J.Lazar, Y.Pu, V.E.Marquez, and P.M.Blumberg (2008).
Characterization of the interaction of phorbol esters with the C1 domain of MRCK (myotonic dystrophy kinase-related Cdc42 binding kinase) alpha/beta.
  J Biol Chem, 283, 10543-10549.  
18640982 W.Wen, W.Liu, J.Yan, and M.Zhang (2008).
Structure basis and unconventional lipid membrane binding properties of the PH-C1 tandem of rho kinases.
  J Biol Chem, 283, 26263-26273.  
17071619 D.R.Dries, L.L.Gallegos, and A.C.Newton (2007).
A single residue in the C1 domain sensitizes novel protein kinase C isoforms to cellular diacylglycerol production.
  J Biol Chem, 282, 826-830.  
17911109 E.Merino, M.A.Sanjuán, I.Moraga, A.Ciprés, and I.Mérida (2007).
Role of the diacylglycerol kinase alpha-conserved domains in membrane targeting in intact T cells.
  J Biol Chem, 282, 35396-35404.  
17656577 F.He, T.Umehara, K.Tsuda, M.Inoue, T.Kigawa, T.Matsuda, T.Yabuki, M.Aoki, E.Seki, T.Terada, M.Shirouzu, A.Tanaka, S.Sugano, Y.Muto, and S.Yokoyama (2007).
Solution structure of the zinc finger HIT domain in protein FON.
  Protein Sci, 16, 1577-1587.
PDB code: 1x4s
17492704 G.Hirai, T.Shimizu, T.Watanabe, Y.Ogoshi, M.Ohkubo, and M.Sodeoka (2007).
Importance of Interaction between C1 Domain and Lipids in Protein Kinase Calpha Activation: Hydrophobic Side Chain Direction in Isobenzofuranone Ligands Controls Enzyme Activation Level.
  ChemMedChem, 2, 1006-1009.  
17728253 H.Feng, M.Ren, L.Chen, and C.S.Rubin (2007).
Properties, regulation, and in vivo functions of a novel protein kinase D: Caenorhabditis elegans DKF-2 links diacylglycerol second messenger to the regulation of stress responses and life span.
  J Biol Chem, 282, 31273-31288.  
17237773 H.Y.Yu, and W.M.Bement (2007).
Control of local actin assembly by membrane fusion-dependent compartment mixing.
  Nat Cell Biol, 9, 149-159.  
17157506 S.Carrasco, and I.Mérida (2007).
Diacylglycerol, when simplicity becomes complex.
  Trends Biochem Sci, 32, 27-36.  
17580120 V.Kheifets, and D.Mochly-Rosen (2007).
Insight into intra- and inter-molecular interactions of PKC: design of specific modulators of kinase function.
  Pharmacol Res, 55, 467-476.  
16698549 E.Harjes, S.Harjes, S.Wohlgemuth, K.H.Müller, E.Krieger, C.Herrmann, and P.Bayer (2006).
GTP-Ras disrupts the intramolecular complex of C1 and RA domains of Nore1.
  Structure, 14, 881-888.
PDB code: 2fnf
16613842 H.Feng, M.Ren, and C.S.Rubin (2006).
Conserved domains subserve novel mechanisms and functions in DKF-1, a Caenorhabditis elegans protein kinase D.
  J Biol Chem, 281, 17815-17826.  
16987023 I.Korichneva (2006).
Zinc dynamics in the myocardial redox signaling network.
  Antioxid Redox Signal, 8, 1707-1721.  
16943444 J.Das, X.Zhou, and K.W.Miller (2006).
Identification of an alcohol binding site in the first cysteine-rich domain of protein kinase Cdelta.
  Protein Sci, 15, 2107-2119.  
16616874 J.H.Hurley (2006).
Membrane binding domains.
  Biochim Biophys Acta, 1761, 805-811.  
17441066 K.Yamatsugu, R.Motoki, M.Kanai, and M.Shibasaki (2006).
Identification of potent, selective protein kinase C inhibitors based on a phorbol skeleton.
  Chem Asian J, 1, 314-321.  
16941159 M.Sato (2006).
Imaging molecular events in single living cells.
  Anal Bioanal Chem, 386, 435-443.  
16585509 R.Alvarez-Venegas, M.Sadder, A.Hlavacka, F.Baluska, Y.Xia, G.Lu, A.Firsov, G.Sarath, H.Moriyama, J.G.Dubrovsky, and Z.Avramova (2006).
The Arabidopsis homolog of trithorax, ATX1, binds phosphatidylinositol 5-phosphate, and the two regulate a common set of target genes.
  Proc Natl Acad Sci U S A, 103, 6049-6054.  
16391233 R.McMullan, E.Hiley, P.Morrison, and S.J.Nurrish (2006).
Rho is a presynaptic activator of neurotransmitter release at pre-existing synapses in C. elegans.
  Genes Dev, 20, 65-76.  
16396605 S.Kocanova, T.Hornakova, J.Hritz, D.Jancura, D.Chorvat, A.Mateasik, J.Ulicny, M.Refregiers, J.C.Maurizot, and P.Miskovsky (2006).
Characterization of the interaction of hypericin with protein kinase C in U-87 MG human glioma cells.
  Photochem Photobiol, 82, 720-728.  
17075264 T.Yamaguchi, M.Suzuki, H.Kimura, and M.Kato (2006).
Role of protein kinase C in eosinophil function.
  Allergol Int, 55, 245-252.  
16950780 Y.Pu, M.L.Peach, S.H.Garfield, S.Wincovitch, V.E.Marquez, and P.M.Blumberg (2006).
Effects on ligand interaction and membrane translocation of the positively charged arginine residues situated along the C1 domain binding cleft in the atypical protein kinase C isoforms.
  J Biol Chem, 281, 33773-33788.  
15591313 B.Hoyos, S.Jiang, and U.Hammerling (2005).
Location and functional significance of retinol-binding sites on the serine/threonine kinase, c-Raf.
  J Biol Chem, 280, 6872-6878.  
15817391 C.Hall, L.Lim, and T.Leung (2005).
C1, see them all.
  Trends Biochem Sci, 30, 169-171.  
  19641676 I.Korichneva (2005).
Redox regulation of cardiac protein kinase C.
  Exp Clin Cardiol, 10, 256-261.  
16150972 I.P.Sugár, N.K.Mizuno, and H.L.Brockman (2005).
Peripheral protein adsorption to lipid-water interfaces: the free area theory.
  Biophys J, 89, 3997-4005.  
16134942 J.H.Kang, M.L.Peach, Y.Pu, N.E.Lewin, M.C.Nicklaus, P.M.Blumberg, and V.E.Marquez (2005).
Conformationally constrained analogues of diacylglycerol (DAG). 25. Exploration of the sn-1 and sn-2 carbonyl functionality reveals the essential role of the sn-1 carbonyl at the lipid interface in the binding of DAG-lactones to protein kinase C.
  J Med Chem, 48, 5738-5748.  
16338787 J.L.Oliva, E.M.Griner, and M.G.Kazanietz (2005).
PKC isozymes and diacylglycerol-regulated proteins as effectors of growth factor receptors.
  Growth Factors, 23, 245-252.  
16041745 K.Irie, Y.Nakagawa, and H.Ohigashi (2005).
Toward the development of new medicinal leads with selectivity for protein kinase C isozymes.
  Chem Rec, 5, 185-195.  
15718244 M.Ling, U.Trollér, R.Zeidman, H.Stensman, A.Schultz, and C.Larsson (2005).
Identification of conserved amino acids N-terminal of the PKC epsilon C1b domain crucial for protein kinase C epsilon-mediated induction of neurite outgrowth.
  J Biol Chem, 280, 17910-17919.  
16079140 R.V.Stahelin, J.Wang, N.R.Blatner, J.D.Rafter, D.Murray, and W.Cho (2005).
The origin of C1A-C2 interdomain interactions in protein kinase Calpha.
  J Biol Chem, 280, 36452-36463.  
15869386 W.Cho, and R.V.Stahelin (2005).
Membrane-protein interactions in cell signaling and membrane trafficking.
  Annu Rev Biophys Biomol Struct, 34, 119-151.  
15923197 Y.Pu, N.A.Perry, D.Yang, N.E.Lewin, N.Kedei, D.C.Braun, S.H.Choi, P.M.Blumberg, S.H.Garfield, J.C.Stone, D.Duan, and V.E.Marquez (2005).
A novel diacylglycerol-lactone shows marked selectivity in vitro among C1 domains of protein kinase C (PKC) isoforms alpha and delta as well as selectivity for RasGRP compared with PKCalpha.
  J Biol Chem, 280, 27329-27338.  
15145947 A.Schultz, M.Ling, and C.Larsson (2004).
Identification of an amino acid residue in the protein kinase C C1b domain crucial for its localization to the Golgi network.
  J Biol Chem, 279, 31750-31760.  
15507211 B.Canagarajah, F.C.Leskow, J.Y.Ho, H.Mischak, L.F.Saidi, M.G.Kazanietz, and J.H.Hurley (2004).
Structural mechanism for lipid activation of the Rac-specific GAP, beta2-chimaerin.
  Cell, 119, 407-418.
PDB code: 1xa6
15234976 J.Das, G.H.Addona, W.S.Sandberg, S.S.Husain, T.Stehle, and K.W.Miller (2004).
Identification of a general anesthetic binding site in the diacylglycerol-binding domain of protein kinase Cdelta.
  J Biol Chem, 279, 37964-37972.  
15576038 M.D.Tibbetts, E.N.Shiozaki, L.Gu, E.R.McDonald, W.S.El-Deiry, and Y.Shi (2004).
Crystal structure of a FYVE-type zinc finger domain from the caspase regulator CARP2.
  Structure, 12, 2257-2263.
PDB code: 1y02
15105418 R.V.Stahelin, M.A.Digman, M.Medkova, B.Ananthanarayanan, J.D.Rafter, H.R.Melowic, and W.Cho (2004).
Mechanism of diacylglycerol-induced membrane targeting and activation of protein kinase Cdelta.
  J Biol Chem, 279, 29501-29512.  
15064353 S.Carrasco, and I.Merida (2004).
Diacylglycerol-dependent binding recruits PKCtheta and RasGRP1 C1 domains to specific subcellular localizations in living T lymphocytes.
  Mol Biol Cell, 15, 2932-2942.  
12954613 B.Ananthanarayanan, R.V.Stahelin, M.A.Digman, and W.Cho (2003).
Activation mechanisms of conventional protein kinase C isoforms are determined by the ligand affinity and conformational flexibility of their C1 domains.
  J Biol Chem, 278, 46886-46894.  
12814644 B.R.Lentz (2003).
Exposure of platelet membrane phosphatidylserine regulates blood coagulation.
  Prog Lipid Res, 42, 423-438.  
12644968 D.H.Chen, Z.Brkanac, C.L.Verlinde, X.J.Tan, L.Bylenok, D.Nochlin, M.Matsushita, H.Lipe, J.Wolff, M.Fernandez, P.J.Cimino, T.D.Bird, and W.H.Raskind (2003).
Missense mutations in the regulatory domain of PKC gamma: a new mechanism for dominant nonepisodic cerebellar ataxia.
  Am J Hum Genet, 72, 839-849.  
12941954 D.Hahn, A.Pischitzis, S.Roesmann, M.K.Hansen, B.Leuenberger, U.Luginbuehl, and E.E.Sterchi (2003).
Phorbol 12-myristate 13-acetate-induced ectodomain shedding and phosphorylation of the human meprinbeta metalloprotease.
  J Biol Chem, 278, 42829-42839.  
12711617 E.M.Silinsky, and T.J.Searl (2003).
Phorbol esters and neurotransmitter release: more than just protein kinase C?
  Br J Pharmacol, 138, 1191-1201.  
12485398 J.G.Dai, and K.Murakami (2003).
Constitutively and autonomously active protein kinase C associated with 14-3-3 zeta in the rodent brain.
  J Neurochem, 84, 23-34.  
14528311 M.Sato, Y.Ueda, T.Takagi, and Y.Umezawa (2003).
Production of PtdInsP3 at endomembranes is triggered by receptor endocytosis.
  Nat Cell Biol, 5, 1016-1022.  
12621060 M.Shindo, K.Irie, A.Masuda, H.Ohigashi, Y.Shirai, K.Miyasaka, and N.Saito (2003).
Synthesis and phorbol ester binding of the cysteine-rich domains of diacylglycerol kinase (DGK) isozymes. DGKgamma and DGKbeta are new targets of tumor-promoting phorbol esters.
  J Biol Chem, 278, 18448-18454.  
12842914 N.Kinoshita, H.Iioka, A.Miyakoshi, and N.Ueno (2003).
PKC delta is essential for Dishevelled function in a noncanonical Wnt pathway that regulates Xenopus convergent extension movements.
  Genes Dev, 17, 1663-1676.  
11964256 A.S.Solodukhin, H.L.Caldwell, J.J.Sando, and R.H.Kretsinger (2002).
Two-dimensional crystal structures of protein kinase C-delta, its regulatory domain, and the enzyme complexed with myelin basic protein.
  Biophys J, 82, 2700-2708.  
12047871 G.Scapin (2002).
Structural biology in drug design: selective protein kinase inhibitors.
  Drug Discov Today, 7, 601-611.  
12213816 I.Korichneva, B.Hoyos, R.Chua, E.Levi, and U.Hammerling (2002).
Zinc release from protein kinase C as the common event during activation by lipid second messenger or reactive oxygen.
  J Biol Chem, 277, 44327-44331.  
12191619 K.Irie, A.Nakahara, Y.Nakagawa, H.Ohigashi, M.Shindo, H.Fukuda, H.Konishi, U.Kikkawa, K.Kashiwagi, and N.Saito (2002).
Establishment of a binding assay for protein kinase C isozymes using synthetic C1 peptides and development of new medicinal leads with protein kinase C isozyme and C1 domain selectivity.
  Pharmacol Ther, 93, 271-281.  
11995919 K.Takahashi, S.Suzuki, Y.Hano, and T.Nomura (2002).
Protein kinase C activation by iridal type triterpenoids.
  Biol Pharm Bull, 25, 432-436.  
12149258 P.Pinton, T.Tsuboi, E.K.Ainscow, T.Pozzan, R.Rizzuto, and G.A.Rutter (2002).
Dynamics of glucose-induced membrane recruitment of protein kinase C beta II in living pancreatic islet beta-cells.
  J Biol Chem, 277, 37702-37710.  
12006563 R.V.Stahelin, F.Long, K.Diraviyam, K.S.Bruzik, D.Murray, and W.Cho (2002).
Phosphatidylinositol 3-phosphate induces the membrane penetration of the FYVE domains of Vps27p and Hrs.
  J Biol Chem, 277, 26379-26388.  
11850425 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 (2002).
Regulation of PKC alpha activity by C1-C2 domain interactions.
  J Biol Chem, 277, 15277-15285.  
12134072 T.Bondeva, A.Balla, P.Várnai, and T.Balla (2002).
Structural determinants of Ras-Raf interaction analyzed in live cells.
  Mol Biol Cell, 13, 2323-2333.  
12015310 T.Santos, S.Carrasco, D.R.Jones, I.Mérida, and A.Eguinoa (2002).
Dynamics of diacylglycerol kinase zeta translocation in living T-cells. Study of the structural domain requirements for translocation and activity.
  J Biol Chem, 277, 30300-30309.  
12211014 T.Simonson, and N.Calimet (2002).
Cys(x)His(y)-Zn2+ interactions: thiol vs. thiolate coordination.
  Proteins, 49, 37-48.  
11173496 E.Ennifar, P.Walter, and P.Dumas (2001).
An efficient method for solving RNA structures: MAD phasing by replacing magnesium with zinc.
  Acta Crystallogr D Biol Crystallogr, 57, 330-332.  
11384750 E.Kerkhoff, and U.R.Rapp (2001).
The Ras-Raf relationship: an unfinished puzzle.
  Adv Enzyme Regul, 41, 261-267.  
11509231 F.Codazzi, M.N.Teruel, and T.Meyer (2001).
Control of astrocyte Ca(2+) oscillations and waves by oscillating translocation and activation of protein kinase C.
  Curr Biol, 11, 1089-1097.  
11514226 M.Blanco-Molina, G.C.Tron, A.Macho, C.Lucena, M.A.Calzado, E.Muñoz, and G.Appendino (2001).
Ingenol esters induce apoptosis in Jurkat cells through an AP-1 and NF-kappaB independent pathway.
  Chem Biol, 8, 767-778.  
11292843 N.V.Grishin (2001).
Treble clef finger--a functionally diverse zinc-binding structural motif.
  Nucleic Acids Res, 29, 1703-1714.  
11284700 S.J.Slater, J.L.Seiz, B.A.Stagliano, and C.D.Stubbs (2001).
Interaction of protein kinase C isozymes with Rho GTPases.
  Biochemistry, 40, 4437-4445.  
11325717 S.L.Robia, J.Ghanta, V.G.Robu, and J.W.Walker (2001).
Localization and kinetics of protein kinase C-epsilon anchoring in cardiac myocytes.
  Biophys J, 80, 2140-2151.  
11689438 Y.Maeda, G.V.Beznoussenko, J.Van Lint, A.A.Mironov, and V.Malhotra (2001).
Recruitment of protein kinase D to the trans-Golgi network via the first cysteine-rich domain.
  EMBO J, 20, 5982-5990.  
10673441 A.Dessen (2000).
Phospholipase A(2) enzymes: structural diversity in lipid messenger metabolism.
  Structure, 8, R15-R22.  
10993914 B.Hoyos, A.Imam, R.Chua, C.Swenson, G.X.Tong, E.Levi, N.Noy, and U.Hämmerling (2000).
The cysteine-rich regions of the regulatory domains of Raf and protein kinase C as retinoid receptors.
  J Exp Med, 192, 835-845.  
10985781 J.E.Johnson, J.Giorgione, and A.C.Newton (2000).
The C1 and C2 domains of protein kinase C are independent membrane targeting modules, with specificity for phosphatidylserine conferred by the C1 domain.
  Biochemistry, 39, 11360-11369.  
10940243 J.H.Hurley, and S.Misra (2000).
Signaling and subcellular targeting by membrane-binding domains.
  Annu Rev Biophys Biomol Struct, 29, 49-79.  
10820483 M.G.Kazanietz (2000).
Eyes wide shut: protein kinase C isozymes are not the only receptors for the phorbol ester tumor promoters.
  Mol Carcinog, 28, 5.  
11018476 P.Conesa-Zamora, J.C.Gómez-Fernández, and S.Corbalán-García (2000).
The C2 domain of protein kinase calpha is directly involved in the diacylglycerol-dependent binding of the C1 domain to the membrane.
  Biochim Biophys Acta, 1487, 246-254.  
10666595 P.D.Sun, and C.H.Hammer (2000).
Mass-spectrometry assisted heavy-atom derivative screening of human Fc gamma RIII crystals.
  Acta Crystallogr D Biol Crystallogr, 56, 161-168.  
10766849 Q.J.Wang, T.W.Fang, D.Fenick, S.Garfield, B.Bienfait, V.E.Marquez, and P.M.Blumberg (2000).
The lipophilicity of phorbol esters as a critical factor in determining the pattern of translocation of protein kinase C delta fused to green fluorescent protein.
  J Biol Chem, 275, 12136-12146.  
10924854 R.Gopalakrishna, and S.Jaken (2000).
Protein kinase C signaling and oxidative stress.
  Free Radic Biol Med, 28, 1349-1361.  
10636245 Y.Endo, and A.Yokoyama (2000).
Role of the hydrophobic moiety of tumor promoters. Synthesis and activity of 2-alkylated benzolactams.
  Bioorg Med Chem Lett, 10, 63-66.  
10092600 A.Hausser, P.Storz, G.Link, H.Stoll, Y.C.Liu, A.Altman, K.Pfizenmaier, and F.J.Johannes (1999).
Protein kinase C mu is negatively regulated by 14-3-3 signal transduction proteins.
  J Biol Chem, 274, 9258-9264.  
10037738 A.S.Edwards, M.C.Faux, J.D.Scott, and A.C.Newton (1999).
Carboxyl-terminal phosphorylation regulates the function and subcellular localization of protein kinase C betaII.
  J Biol Chem, 274, 6461-6468.  
10498194 K.Irie, A.Nakahara, H.Ohigashi, H.Fukuda, P.A.Wender, H.Konishi, and U.Kikkawa (1999).
Synthesis and phorbol ester-binding studies of the individual cysteine-rich motifs of protein kinase D.
  Bioorg Med Chem Lett, 9, 2487-2490.  
  10422841 K.M.Boeshans, K.A.Resing, J.B.Hunt, N.G.Ahn, and J.B.Shabb (1999).
Structural characterization of the membrane-associated regulatory subunit of type I cAMP-dependent protein kinase by mass spectrometry: identification of Ser81 as the in vivo phosphorylation site of RIalpha.
  Protein Sci, 8, 1515-1522.  
10085132 L.Stempka, M.Schnölzer, S.Radke, G.Rincke, F.Marks, and M.Gschwendt (1999).
Requirements of protein kinase cdelta for catalytic function. Role of glutamic acid 500 and autophosphorylation on serine 643.
  J Biol Chem, 274, 8886-8892.  
  10373555 M.Andjelković, S.M.Maira, P.Cron, P.J.Parker, and B.A.Hemmings (1999).
Domain swapping used to investigate the mechanism of protein kinase B regulation by 3-phosphoinositide-dependent protein kinase 1 and Ser473 kinase.
  Mol Cell Biol, 19, 5061-5072.  
10092837 M.Gschwendt (1999).
Protein kinase C delta.
  Eur J Biochem, 259, 555-564.  
10518540 M.J.Caloca, M.L.Garcia-Bermejo, P.M.Blumberg, N.E.Lewin, E.Kremmer, H.Mischak, S.Wang, K.Nacro, B.Bienfait, V.E.Marquez, and M.G.Kazanietz (1999).
beta2-chimaerin is a novel target for diacylglycerol: binding properties and changes in subcellular localization mediated by ligand binding to its C1 domain.
  Proc Natl Acad Sci U S A, 96, 11854-11859.  
10391930 M.Medkova, and W.Cho (1999).
Interplay of C1 and C2 domains of protein kinase C-alpha in its membrane binding and activation.
  J Biol Chem, 274, 19852-19861.  
10601287 Q.J.Wang, D.Bhattacharyya, S.Garfield, K.Nacro, V.E.Marquez, and P.M.Blumberg (1999).
Differential localization of protein kinase C delta by phorbol esters and related compounds using a fusion protein with green fluorescent protein.
  J Biol Chem, 274, 37233-37239.  
10090770 S.J.Slater, S.K.Milano, B.A.Stagliano, K.J.Gergich, C.Ho, A.Mazurek, F.J.Taddeo, M.B.Kelly, M.D.Yeager, and C.D.Stubbs (1999).
Synergistic activation of protein kinase Calpha, -betaI, and -gamma isoforms induced by diacylglycerol and phorbol ester: roles of membrane association and activating conformational changes.
  Biochemistry, 38, 3804-3815.  
10367894 S.Misra, and J.H.Hurley (1999).
Crystal structure of a phosphatidylinositol 3-phosphate-specific membrane-targeting motif, the FYVE domain of Vps27p.
  Cell, 97, 657-666.
PDB code: 1vfy
10454202 V.E.Marquez, K.Nacro, S.Benzaria, J.Lee, R.Sharma, K.Teng, G.W.Milne, B.Bienfait, S.Wang, N.E.Lewin, and P.M.Blumberg (1999).
The transition from a pharmacophore-guided approach to a receptor-guided approach in the design of potent protein kinase C ligands.
  Pharmacol Ther, 82, 251-261.  
10498208 Y.Endo, T.Yoshimi, K.Kimura, and A.Itai (1999).
Protein kinase C modulators bearing dicarba-CLOSO-dodecaborane as a hydrophobic pharmacophore.
  Bioorg Med Chem Lett, 9, 2561-2564.  
9535877 A.M.Parissenti, A.F.Kirwan, S.A.Kim, C.M.Colantonio, and B.P.Schimmer (1998).
Inhibitory properties of the regulatory domains of human protein kinase Calpha and mouse protein kinase Cepsilon.
  J Biol Chem, 273, 8940-8945.  
  9819387 C.E.Tognon, H.E.Kirk, L.A.Passmore, I.P.Whitehead, C.J.Der, and R.J.Kay (1998).
Regulation of RasGRP via a phorbol ester-responsive C1 domain.
  Mol Cell Biol, 18, 6995-7008.  
9456311 E.Oancea, M.N.Teruel, A.F.Quest, and T.Meyer (1998).
Green fluorescent protein (GFP)-tagged cysteine-rich domains from protein kinase C as fluorescent indicators for diacylglycerol signaling in living cells.
  J Cell Biol, 140, 485-498.  
9565359 H.E.Porritt, K.L.Anderson, R.K.Suniara, E.J.Jenkinson, and J.J.Owen (1998).
Cellular interactions in the thymus regulate the protein kinase C signaling pathway.
  Eur J Immunol, 28, 1197-1203.  
9687370 H.Pappa, J.Murray-Rust, L.V.Dekker, P.J.Parker, and N.Q.McDonald (1998).
Crystal structure of the C2 domain from protein kinase C-delta.
  Structure, 6, 885-894.
PDB code: 1bdy
  10082367 I.L.Alberts, K.Nadassy, and S.J.Wodak (1998).
Analysis of zinc binding sites in protein crystal structures.
  Protein Sci, 7, 1700-1716.  
9724512 J.E.Johnson, M.L.Zimmerman, D.L.Daleke, and A.C.Newton (1998).
Lipid structure and not membrane structure is the major determinant in the regulation of protein kinase C by phosphatidylserine.
  Biochemistry, 37, 12020-12025.  
9852057 J.J.Sando, O.I.Chertihin, J.M.Owens, and R.H.Kretsinger (1998).
Contributions to maxima in protein kinase C activation.
  J Biol Chem, 273, 34022-34027.  
9478126 J.P.Mackay, and M.Crossley (1998).
Zinc fingers are sticking together.
  Trends Biochem Sci, 23, 1-4.  
9760249 L.Lichtenbergova, E.T.Yoon, and W.Cho (1998).
Membrane penetration of cytosolic phospholipase A2 is necessary for its interfacial catalysis and arachidonate specificity.
  Biochemistry, 37, 14128-14136.  
  9774683 M.Daub, J.Jöckel, T.Quack, C.K.Weber, F.Schmitz, U.R.Rapp, A.Wittinghofer, and C.Block (1998).
The RafC1 cysteine-rich domain contains multiple distinct regulatory epitopes which control Ras-dependent Raf activation.
  Mol Cell Biol, 18, 6698-6710.  
9651347 M.Medkova, and W.Cho (1998).
Mutagenesis of the C2 domain of protein kinase C-alpha. Differential roles of Ca2+ ligands and membrane binding residues.
  J Biol Chem, 273, 17544-17552.  
9538007 M.Medkova, and W.Cho (1998).
Differential membrane-binding and activation mechanisms of protein kinase C-alpha and -epsilon.
  Biochemistry, 37, 4892-4900.  
9860841 M.Mosior, and A.C.Newton (1998).
Mechanism of the apparent cooperativity in the interaction of protein kinase C with phosphatidylserine.
  Biochemistry, 37, 17271-17279.  
9575216 N.E.Ward, D.S.Pierce, S.E.Chung, K.R.Gravitt, and C.A.O'Brian (1998).
Irreversible inactivation of protein kinase C by glutathione.
  J Biol Chem, 273, 12558-12566.  
9817842 R.B.Sutton, and S.R.Sprang (1998).
Structure of the protein kinase Cbeta phospholipid-binding C2 domain complexed with Ca2+.
  Structure, 6, 1395-1405.
PDB code: 1a25
9722545 S.J.Slater, F.J.Taddeo, A.Mazurek, B.A.Stagliano, S.K.Milano, M.B.Kelly, C.Ho, and C.D.Stubbs (1998).
Inhibition of membrane lipid-independent protein kinase Calpha activity by phorbol esters, diacylglycerols, and bryostatin-1.
  J Biol Chem, 273, 23160-23168.  
9873429 V.E.Marquez, R.Sharma, S.Wang, N.E.Lewin, P.M.Blumberg, I.S.Kim, and J.Lee (1998).
Conformationally constrained analogues of diacylglycerol (DAG). 14. Dissection of the roles of the sn-1 and sn-2 carbonyls in DAG mimetics by isopharmacophore replacement.
  Bioorg Med Chem Lett, 8, 1757-1762.  
9069266 A.C.Newton (1997).
Regulation of protein kinase C.
  Curr Opin Cell Biol, 9, 161-167.  
9382829 H.Bayley (1997).
Toxin structure: part of a hole?
  Curr Biol, 7, R763-R767.  
  9041654 J.H.Hurley, A.C.Newton, P.J.Parker, P.M.Blumberg, and Y.Nishizuka (1997).
Taxonomy and function of C1 protein kinase C homology domains.
  Protein Sci, 6, 477-480.  
9266179 J.H.Hurley, and J.A.Grobler (1997).
Protein kinase C and phospholipase C: bilayer interactions and regulation.
  Curr Opin Struct Biol, 7, 557-565.  
9295346 J.L.Zugaza, R.T.Waldron, J.Sinnett-Smith, and E.Rozengurt (1997).
Bombesin, vasopressin, endothelin, bradykinin, and platelet-derived growth factor rapidly activate protein kinase D through a protein kinase C-dependent signal transduction pathway.
  J Biol Chem, 272, 23952-23960.  
9305890 J.Saras, P.Franzén, P.Aspenström, U.Hellman, L.J.Gonez, and C.H.Heldin (1997).
A novel GTPase-activating protein for Rho interacts with a PDZ domain of the protein-tyrosine phosphatase PTPL1.
  J Biol Chem, 272, 24333-24338.  
9313873 K.Irie, Y.Yanai, K.Oie, J.Ishizawa, Y.Nakagawa, H.Ohigashi, P.A.Wender, and U.Kikkawa (1997).
Comparison of chemical characteristics of the first and the second cysteine-rich domains of protein kinase C gamma.
  Bioorg Med Chem, 5, 1725-1737.  
  9253765 M.Mosior, and R.M.Epand (1997).
Protein kinase C: an example of a calcium-regulated protein binding to membranes (review).
  Mol Membr Biol, 14, 65-70.  
9371754 N.R.Michaud, M.Therrien, A.Cacace, L.C.Edsall, S.Spiegel, G.M.Rubin, and D.K.Morrison (1997).
KSR stimulates Raf-1 activity in a kinase-independent manner.
  Proc Natl Acad Sci U S A, 94, 12792-12796.  
9268359 P.Acs, K.Bögi, P.S.Lorenzo, A.M.Marquez, T.Bíró, Z.Szállási, and P.M.Blumberg (1997).
The catalytic domain of protein kinase C chimeras modulates the affinity and targeting of phorbol ester-induced translocation.
  J Biol Chem, 272, 22148-22153.  
9353351 P.Acs, Q.J.Wang, K.Bögi, A.M.Marquez, P.S.Lorenzo, T.Bíró, Z.Szállási, J.F.Mushinski, and P.M.Blumberg (1997).
Both the catalytic and regulatory domains of protein kinase C chimeras modulate the proliferative properties of NIH 3T3 cells.
  J Biol Chem, 272, 28793-28799.  
9271501 R.X.Xu, T.Pawelczyk, T.H.Xia, and S.C.Brown (1997).
NMR structure of a protein kinase C-gamma phorbol-binding domain and study of protein-lipid micelle interactions.
  Biochemistry, 36, 10709-10717.
PDB codes: 1tbn 1tbo
9054438 Y.Izumi, S.Hirai, Y.Tamai, A.Fujise-Matsuoka, Y.Nishimura, and S.Ohno (1997).
A protein kinase Cdelta-binding protein SRBC whose expression is induced by serum starvation.
  J Biol Chem, 272, 7381-7389.  
  8972184 Z.Luo, B.Diaz, M.S.Marshall, and J.Avruch (1997).
An intact Raf zinc finger is required for optimal binding to processed Ras and for ras-dependent Raf activation in situ.
  Mol Cell Biol, 17, 46-53.  
8889163 A.R.Dibble, A.K.Hinderliter, J.J.Sando, and R.L.Biltonen (1996).
Lipid lateral heterogeneity in phosphatidylcholine/phosphatidylserine/diacylglycerol vesicles and its influence on protein kinase C activation.
  Biophys J, 71, 1877-1890.  
8973661 G.Krauter, C.W.Von der Lieth, R.Schmidt, and E.Hecker (1996).
Structure/activity relationships of polyfunctional diterpenes of the tigliane type. A pharmacophore model for protein-kinase-C activators based on structure/activity studies and molecular modeling of the tumor promoters 12-O-tetradecanoylphorbol 13-acetate and 3-O-tetradecanoylingenol.
  Eur J Biochem, 242, 417-427.  
8710867 H.R.Mott, J.W.Carpenter, S.Zhong, S.Ghosh, R.M.Bell, and S.L.Campbell (1996).
The solution structure of the Raf-1 cysteine-rich domain: a novel ras and phospholipid binding site.
  Proc Natl Acad Sci U S A, 93, 8312-8317.
PDB codes: 1faq 1far
8913682 H.S.Pappa, A.E.Stewart, and N.Q.McDonald (1996).
Incorporating anomalous scattering centres into macromolecules.
  Curr Opin Struct Biol, 6, 611-616.  
8798641 H.Stenmark, R.Aasland, B.H.Toh, and A.D'Arrigo (1996).
Endosomal localization of the autoantigen EEA1 is mediated by a zinc-binding FYVE finger.
  J Biol Chem, 271, 24048-24054.  
  8947045 J.L.Zugaza, J.Sinnett-Smith, J.Van Lint, and E.Rozengurt (1996).
Protein kinase D (PKD) activation in intact cells through a protein kinase C-dependent signal transduction pathway.
  EMBO J, 15, 6220-6230.  
8702546 L.P.Hammonds-Odie, T.R.Jackson, A.A.Profit, I.J.Blader, C.W.Turck, G.D.Prestwich, and A.B.Theibert (1996).
Identification and cloning of centaurin-alpha. A novel phosphatidylinositol 3,4,5-trisphosphate-binding protein from rat brain.
  J Biol Chem, 271, 18859-18868.  
8634293 M.Mosior, and A.C.Newton (1996).
Calcium-independent binding to interfacial phorbol esters causes protein kinase C to associate with membranes in the absence of acidic lipids.
  Biochemistry, 35, 1612-1623.  
  8960355 M.P.Walsh, A.Horowitz, O.Clément-Chomienne, J.E.Andrea, B.G.Allen, and K.G.Morgan (1996).
Protein kinase C mediation of Ca(2+)-independent contractions of vascular smooth muscle.
  Biochem Cell Biol, 74, 485-502.  
8703966 R.S.Arnold, and R.B.Cornell (1996).
Lipid regulation of CTP: phosphocholine cytidylyltransferase: electrostatic, hydrophobic, and synergistic interactions of anionic phospholipids and diacylglycerol.
  Biochemistry, 35, 9917-9924.  
8617724 S.J.Slater, C.Ho, M.B.Kelly, J.D.Larkin, F.J.Taddeo, M.D.Yeager, and C.D.Stubbs (1996).
Protein kinase Calpha contains two activator binding sites that bind phorbol esters and diacylglycerols with opposite affinities.
  J Biol Chem, 271, 4627-4631.  
8791422 S.Spiegel, D.Foster, and R.Kolesnick (1996).
Signal transduction through lipid second messengers.
  Curr Opin Cell Biol, 8, 159-167.  
  8617235 T.Ishizaki, M.Maekawa, K.Fujisawa, K.Okawa, A.Iwamatsu, A.Fujita, N.Watanabe, Y.Saito, A.Kakizuka, N.Morii, and S.Narumiya (1996).
The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase.
  EMBO J, 15, 1885-1893.  
8702685 T.M.Klauck, X.Xu, B.Mousseau, and S.Jaken (1996).
Cloning and characterization of a glucocorticoid-induced diacylglycerol kinase.
  J Biol Chem, 271, 19781-19788.  
8702464 Z.Szallasi, K.Bogi, S.Gohari, T.Biro, P.Acs, and P.M.Blumberg (1996).
Non-equivalent roles for the first and second zinc fingers of protein kinase Cdelta. Effect of their mutation on phorbol ester-induced translocation in NIH 3T3 cells.
  J Biol Chem, 271, 18299-18301.  
  7499357 A.C.Newton (1995).
Protein kinase C: structure, function, and regulation.
  J Biol Chem, 270, 28495-28498.  
8548282 B.Bax, and H.Jhoti (1995).
Protein-protein interactions. Putting the pieces together.
  Curr Biol, 5, 1119-1121.  
7665608 M.G.Kazanietz, S.Wang, G.W.Milne, N.E.Lewin, H.L.Liu, and P.M.Blumberg (1995).
Residues in the second cysteine-rich region of protein kinase C delta relevant to phorbol ester binding as revealed by site-directed mutagenesis.
  J Biol Chem, 270, 21852-21859.  
7592722 M.Mosior, and A.C.Newton (1995).
Mechanism of interaction of protein kinase C with phorbol esters. Reversibility and nature of membrane association.
  J Biol Chem, 270, 25526-25533.  
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