Skip to main content
PMC home page
Protein Science : A Publication of the Protein Society logoLink to Protein Science : A Publication of the Protein Society
. 1996 Jan;5(1):162–166. doi: 10.1002/pro.5560050120

Extending the C2 domain family: C2s in PKCs delta, epsilon, eta, theta, phospholipases, GAPs, and perforin.

C P Ponting 1, P J Parker 1
PMCID: PMC2143250  PMID: 8771209

Abstract

Various membrane lipid metabolites, generated by phospholipases C and D (PLCs, PLDs), are known to regulate the activities of protein kinases C (PKCs) and GTP-ase activating proteins (GAPs) in a range of cellular processes. Conventional Ca(2+)-dependent PKCs (alpha, beta I, beta II, and gamma), PLCs and various GAPs are all known to contain copies of a phospholipid-binding domain, termed C2 or CalB. Here we recognize that C2 domains are also present in "new" Ca(2+)-independent PKCs (delta, epsilon, eta, and theta), other kinases, a eukaryotic PLD, the breakpoint cluster region (BCR) gene product, and two further GAPS. Twenty-two previously unrecognized C2 domain sequences are presented, which include a single copy in the mammalian poreforming proteins, perforin.

Full Text

The Full Text of this article is available as a PDF (3.0 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barton G. J. ALSCRIPT: a tool to format multiple sequence alignments. Protein Eng. 1993 Jan;6(1):37–40. doi: 10.1093/protein/6.1.37. [DOI] [PubMed] [Google Scholar]
  2. Barton G. J. An efficient algorithm to locate all locally optimal alignments between two sequences allowing for gaps. Comput Appl Biosci. 1993 Dec;9(6):729–734. doi: 10.1093/bioinformatics/9.6.729. [DOI] [PubMed] [Google Scholar]
  3. Bazzi M. D., Nelsestuen G. L. Protein kinase C interaction with calcium: a phospholipid-dependent process. Biochemistry. 1990 Aug 21;29(33):7624–7630. doi: 10.1021/bi00485a012. [DOI] [PubMed] [Google Scholar]
  4. Bork P., Sudol M. The WW domain: a signalling site in dystrophin? Trends Biochem Sci. 1994 Dec;19(12):531–533. doi: 10.1016/0968-0004(94)90053-1. [DOI] [PubMed] [Google Scholar]
  5. Brose N., Hofmann K., Hata Y., Südhof T. C. Mammalian homologues of Caenorhabditis elegans unc-13 gene define novel family of C2-domain proteins. J Biol Chem. 1995 Oct 20;270(42):25273–25280. doi: 10.1074/jbc.270.42.25273. [DOI] [PubMed] [Google Scholar]
  6. Dekker L. V., Parker P. J. Protein kinase C--a question of specificity. Trends Biochem Sci. 1994 Feb;19(2):73–77. doi: 10.1016/0968-0004(94)90038-8. [DOI] [PubMed] [Google Scholar]
  7. Fukuda M., Aruga J., Niinobe M., Aimoto S., Mikoshiba K. Inositol-1,3,4,5-tetrakisphosphate binding to C2B domain of IP4BP/synaptotagmin II. J Biol Chem. 1994 Nov 18;269(46):29206–29211. [PubMed] [Google Scholar]
  8. Kiley S., Schaap D., Parker P., Hsieh L. L., Jaken S. Protein kinase C heterogeneity in GH4C1 rat pituitary cells. Characterization of a Ca2(+)-independent phorbol ester receptor. J Biol Chem. 1990 Sep 15;265(26):15704–15712. [PubMed] [Google Scholar]
  9. Kraft A. S., Anderson W. B. Phorbol esters increase the amount of Ca2+, phospholipid-dependent protein kinase associated with plasma membrane. Nature. 1983 Feb 17;301(5901):621–623. doi: 10.1038/301621a0. [DOI] [PubMed] [Google Scholar]
  10. Levin D. E., Fields F. O., Kunisawa R., Bishop J. M., Thorner J. A candidate protein kinase C gene, PKC1, is required for the S. cerevisiae cell cycle. Cell. 1990 Jul 27;62(2):213–224. doi: 10.1016/0092-8674(90)90360-q. [DOI] [PubMed] [Google Scholar]
  11. Li C., Ullrich B., Zhang J. Z., Anderson R. G., Brose N., Südhof T. C. Ca(2+)-dependent and -independent activities of neural and non-neural synaptotagmins. Nature. 1995 Jun 15;375(6532):594–599. doi: 10.1038/375594a0. [DOI] [PubMed] [Google Scholar]
  12. Maekawa M., Li S., Iwamatsu A., Morishita T., Yokota K., Imai Y., Kohsaka S., Nakamura S., Hattori S. A novel mammalian Ras GTPase-activating protein which has phospholipid-binding and Btk homology regions. Mol Cell Biol. 1994 Oct;14(10):6879–6885. doi: 10.1128/mcb.14.10.6879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Müller C., Tschopp J. Resistance of CTL to perforin-mediated lysis. Evidence for a lymphocyte membrane protein interacting with perforin. J Immunol. 1994 Sep 15;153(6):2470–2478. [PubMed] [Google Scholar]
  14. Palmer R. H., Parker P. J. Expression, purification and characterization of the ubiquitous protein kinase C-related kinase 1. Biochem J. 1995 Jul 1;309(Pt 1):315–320. doi: 10.1042/bj3090315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Palmer R. H., Ridden J., Parker P. J. Cloning and expression patterns of two members of a novel protein-kinase-C-related kinase family. Eur J Biochem. 1995 Jan 15;227(1-2):344–351. doi: 10.1111/j.1432-1033.1995.tb20395.x. [DOI] [PubMed] [Google Scholar]
  16. Perin M. S., Fried V. A., Mignery G. A., Jahn R., Südhof T. C. Phospholipid binding by a synaptic vesicle protein homologous to the regulatory region of protein kinase C. Nature. 1990 May 17;345(6272):260–263. doi: 10.1038/345260a0. [DOI] [PubMed] [Google Scholar]
  17. Ponting C. P., Phillips C. DHR domains in syntrophins, neuronal NO synthases and other intracellular proteins. Trends Biochem Sci. 1995 Mar;20(3):102–103. doi: 10.1016/s0968-0004(00)88973-2. [DOI] [PubMed] [Google Scholar]
  18. Sasaki T., Kikuchi A., Araki S., Hata Y., Isomura M., Kuroda S., Takai Y. Purification and characterization from bovine brain cytosol of a protein that inhibits the dissociation of GDP from and the subsequent binding of GTP to smg p25A, a ras p21-like GTP-binding protein. J Biol Chem. 1990 Feb 5;265(4):2333–2337. [PubMed] [Google Scholar]
  19. Sossin W. S., Schwartz J. H. Ca(2+)-independent protein kinase Cs contain an amino-terminal domain similar to the C2 consensus sequence. Trends Biochem Sci. 1993 Jun;18(6):207–208. doi: 10.1016/0968-0004(93)90189-t. [DOI] [PubMed] [Google Scholar]
  20. Stephens L. R., Jackson T. R., Hawkins P. T. Agonist-stimulated synthesis of phosphatidylinositol(3,4,5)-trisphosphate: a new intracellular signalling system? Biochim Biophys Acta. 1993 Oct 7;1179(1):27–75. doi: 10.1016/0167-4889(93)90072-w. [DOI] [PubMed] [Google Scholar]
  21. Sutton R. B., Davletov B. A., Berghuis A. M., Südhof T. C., Sprang S. R. Structure of the first C2 domain of synaptotagmin I: a novel Ca2+/phospholipid-binding fold. Cell. 1995 Mar 24;80(6):929–938. doi: 10.1016/0092-8674(95)90296-1. [DOI] [PubMed] [Google Scholar]
  22. Takai Y., Kishimoto A., Iwasa Y., Kawahara Y., Mori T., Nishizuka Y. Calcium-dependent activation of a multifunctional protein kinase by membrane phospholipids. J Biol Chem. 1979 May 25;254(10):3692–3695. [PubMed] [Google Scholar]
  23. Toda T., Cameron S., Sass P., Wigler M. SCH9, a gene of Saccharomyces cerevisiae that encodes a protein distinct from, but functionally and structurally related to, cAMP-dependent protein kinase catalytic subunits. Genes Dev. 1988 May;2(5):517–527. doi: 10.1101/gad.2.5.517. [DOI] [PubMed] [Google Scholar]
  24. Tsai M. H., Yu C. L., Wei F. S., Stacey D. W. The effect of GTPase activating protein upon ras is inhibited by mitogenically responsive lipids. Science. 1989 Jan 27;243(4890):522–526. doi: 10.1126/science.2536192. [DOI] [PubMed] [Google Scholar]
  25. Wang X., Xu L., Zheng L. Cloning and expression of phosphatidylcholine-hydrolyzing phospholipase D from Ricinus communis L. J Biol Chem. 1994 Aug 12;269(32):20312–20317. [PubMed] [Google Scholar]
  26. Welters P., Takegawa K., Emr S. D., Chrispeels M. J. AtVPS34, a phosphatidylinositol 3-kinase of Arabidopsis thaliana, is an essential protein with homology to a calcium-dependent lipid binding domain. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11398–11402. doi: 10.1073/pnas.91.24.11398. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Protein Science : A Publication of the Protein Society are provided here courtesy of The Protein Society

RESOURCES