Abstract
The ability of individual members of the 14-3-3 protein family to inhibit protein kinase C (PKC) has been studied by using a synthetic peptide based on the specific 80 kDa substrate for PKC (MARCKS protein) in two different assay systems. Recombinant 14-3-3 and isoforms renatured by a novel method after separation by reverse-phase h.p.l.c. were studied. The detailed effects of diacylglycerol and the phorbol ester phorbol 12-myristate 13-acetate on the inhibition were also investigated. This suggests that one of the sites of interaction of 14-3-3 may be the cysteine-rich (C1) domain in PKC. Since a region in secreted phospholipase A2 (PLA2) shares similarity with this domain, the ability of 14-3-3 to interact with mammalian PLA2 was studied. Cytosolic PLA2 has some similarity to the C2 region of PKC, and the effect of 14-3-3 on this class of PLA2 was also analysed. In contrast with a previous report, no PLA2 activity was found in brain 14-3-3, nor in any of the recombinant proteins tested. These include zeta 14-3-3 isoform, on which the original observation was made.
Full text
PDF








Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aitken A., Collinge D. B., van Heusden B. P., Isobe T., Roseboom P. H., Rosenfeld G., Soll J. 14-3-3 proteins: a highly conserved, widespread family of eukaryotic proteins. Trends Biochem Sci. 1992 Dec;17(12):498–501. doi: 10.1016/0968-0004(92)90339-b. [DOI] [PubMed] [Google Scholar]
- Aitken A., Ellis C. A., Harris A., Sellers L. A., Toker A. Kinase and neurotransmitters. Nature. 1990 Apr 12;344(6267):594–594. doi: 10.1038/344594a0. [DOI] [PubMed] [Google Scholar]
- Albert K. A., Wu W. C., Nairn A. C., Greengard P. Inhibition by calmodulin of calcium/phospholipid-dependent protein phosphorylation. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3622–3625. doi: 10.1073/pnas.81.12.3622. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Amess B., Manjarrez-Hernandez H. A., Howell S. A., Learmonth M., Aitken A. Multisite phosphorylation of the 80 kDa (MARCKS) protein kinase C substrate in C3H/10T1/2 fibroblasts. Quantitative analysis of individual sites by solid-phase microsequencing. FEBS Lett. 1992 Feb 10;297(3):285–291. doi: 10.1016/0014-5793(92)80557-w. [DOI] [PubMed] [Google Scholar]
- Balazovich K. J., McEwen E. L., Lutzke M. L., Boxer L. A., White T. Purification of PKC-I, an endogenous protein kinase C inhibitor, and types II and III protein kinase C isoenzymes from human neutrophils. Biochem J. 1992 Jun 1;284(Pt 2):399–405. doi: 10.1042/bj2840399. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berridge M. J. Inositol trisphosphate and calcium signalling. Nature. 1993 Jan 28;361(6410):315–325. doi: 10.1038/361315a0. [DOI] [PubMed] [Google Scholar]
- Boustead C. M., Walker J. H., Geisow M. J. Isolation and characterization of two novel calcium-dependent phospholipid-binding proteins from bovine lung. FEBS Lett. 1988 Jun 20;233(2):233–238. doi: 10.1016/0014-5793(88)80433-2. [DOI] [PubMed] [Google Scholar]
- Brandt J., Thordal-Christensen H., Vad K., Gregersen P. L., Collinge D. B. A pathogen-induced gene of barley encodes a protein showing high similarity to a protein kinase regulator. Plant J. 1992 Sep;2(5):815–820. [PubMed] [Google Scholar]
- Clark J. D., Lin L. L., Kriz R. W., Ramesha C. S., Sultzman L. A., Lin A. Y., Milona N., Knopf J. L. A novel arachidonic acid-selective cytosolic PLA2 contains a Ca(2+)-dependent translocation domain with homology to PKC and GAP. Cell. 1991 Jun 14;65(6):1043–1051. doi: 10.1016/0092-8674(91)90556-e. [DOI] [PubMed] [Google Scholar]
- Clark J. D., Milona N., Knopf J. L. Purification of a 110-kilodalton cytosolic phospholipase A2 from the human monocytic cell line U937. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7708–7712. doi: 10.1073/pnas.87.19.7708. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DOLE V. P. A relation between non-esterified fatty acids in plasma and the metabolism of glucose. J Clin Invest. 1956 Feb;35(2):150–154. doi: 10.1172/JCI103259. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fu H., Coburn J., Collier R. J. The eukaryotic host factor that activates exoenzyme S of Pseudomonas aeruginosa is a member of the 14-3-3 protein family. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2320–2324. doi: 10.1073/pnas.90.6.2320. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Garrigos M., Deschamps S., Viel A., Lund S., Champeil P., Møller J. V., le Maire M. Detection of Ca(2+)-binding proteins by electrophoretic migration in the presence of Ca2+ combined with 45Ca2+ overlay of protein blots. Anal Biochem. 1991 Apr;194(1):82–88. doi: 10.1016/0003-2697(91)90154-l. [DOI] [PubMed] [Google Scholar]
- Hennessey J. P., Jr, Johnson W. C., Jr Information content in the circular dichroism of proteins. Biochemistry. 1981 Mar 3;20(5):1085–1094. doi: 10.1021/bi00508a007. [DOI] [PubMed] [Google Scholar]
- Hirsch S., Aitken A., Bertsch U., Soll J. A plant homologue to mammalian brain 14-3-3 protein and protein kinase C inhibitor. FEBS Lett. 1992 Jan 20;296(2):222–224. doi: 10.1016/0014-5793(92)80384-s. [DOI] [PubMed] [Google Scholar]
- Hug H., Sarre T. F. Protein kinase C isoenzymes: divergence in signal transduction? Biochem J. 1993 Apr 15;291(Pt 2):329–343. doi: 10.1042/bj2910329. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ichimura T., Isobe T., Okuyama T., Takahashi N., Araki K., Kuwano R., Takahashi Y. Molecular cloning of cDNA coding for brain-specific 14-3-3 protein, a protein kinase-dependent activator of tyrosine and tryptophan hydroxylases. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7084–7088. doi: 10.1073/pnas.85.19.7084. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ichimura T., Isobe T., Okuyama T., Yamauchi T., Fujisawa H. Brain 14-3-3 protein is an activator protein that activates tryptophan 5-monooxygenase and tyrosine 3-monooxygenase in the presence of Ca2+,calmodulin-dependent protein kinase II. FEBS Lett. 1987 Jul 13;219(1):79–82. doi: 10.1016/0014-5793(87)81194-8. [DOI] [PubMed] [Google Scholar]
- Ichimura T., Sugano H., Kuwano R., Sunaya T., Okuyama T., Isobe T. Widespread distribution of the 14-3-3 protein in vertebrate brains and bovine tissues: correlation with the distributions of calcium-dependent protein kinases. J Neurochem. 1991 Apr;56(4):1449–1451. doi: 10.1111/j.1471-4159.1991.tb11446.x. [DOI] [PubMed] [Google Scholar]
- Isobe T., Hiyane Y., Ichimura T., Okuyama T., Takahashi N., Nakajo S., Nakaya K. Activation of protein kinase C by the 14-3-3 proteins homologous with Exo1 protein that stimulates calcium-dependent exocytosis. FEBS Lett. 1992 Aug 17;308(2):121–124. doi: 10.1016/0014-5793(92)81257-m. [DOI] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Leffers H., Madsen P., Rasmussen H. H., Honoré B., Andersen A. H., Walbum E., Vandekerckhove J., Celis J. E. Molecular cloning and expression of the transformation sensitive epithelial marker stratifin. A member of a protein family that has been involved in the protein kinase C signalling pathway. J Mol Biol. 1993 Jun 20;231(4):982–998. doi: 10.1006/jmbi.1993.1346. [DOI] [PubMed] [Google Scholar]
- Loeb L. A., Gross R. W. Identification and purification of sheep platelet phospholipase A2 isoforms. Activation by physiologic concentrations of calcium ion. J Biol Chem. 1986 Aug 15;261(23):10467–10470. [PubMed] [Google Scholar]
- Lu G., DeLisle A. J., de Vetten N. C., Ferl R. J. Brain proteins in plants: an Arabidopsis homolog to neurotransmitter pathway activators is part of a DNA binding complex. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11490–11494. doi: 10.1073/pnas.89.23.11490. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Martens G. J., Piosik P. A., Danen E. H. Evolutionary conservation of the 14-3-3 protein. Biochem Biophys Res Commun. 1992 May 15;184(3):1456–1459. doi: 10.1016/s0006-291x(05)80046-4. [DOI] [PubMed] [Google Scholar]
- Martin H., Patel Y., Jones D., Howell S., Robinson K., Aitken A. Antibodies against the major brain isoforms of 14-3-3 protein. An antibody specific for the N-acetylated amino-terminus of a protein. FEBS Lett. 1993 Oct 4;331(3):296–303. doi: 10.1016/0014-5793(93)80356-y. [DOI] [PubMed] [Google Scholar]
- McDonald J. R., Walsh M. P. Ca2+-binding proteins from bovine brain including a potent inhibitor of protein kinase C. Biochem J. 1985 Dec 1;232(2):559–567. doi: 10.1042/bj2320559. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mizushima H., Kudo I., Horigome K., Murakami M., Hayakawa M., Kim D. K., Kondo E., Tomita M., Inoue K. Purification of rabbit platelet secretory phospholipase A2 and its characteristics. J Biochem. 1989 Apr;105(4):520–525. doi: 10.1093/oxfordjournals.jbchem.a122699. [DOI] [PubMed] [Google Scholar]
- Mochly-Rosen D., Khaner H., Lopez J., Smith B. L. Intracellular receptors for activated protein kinase C. Identification of a binding site for the enzyme. J Biol Chem. 1991 Aug 15;266(23):14866–14868. [PubMed] [Google Scholar]
- Morgan A., Burgoyne R. D. Exo1 and Exo2 proteins stimulate calcium-dependent exocytosis in permeabilized adrenal chromaffin cells. Nature. 1992 Feb 27;355(6363):833–836. doi: 10.1038/355833a0. [DOI] [PubMed] [Google Scholar]
- Morgan A., Burgoyne R. D. Interaction between protein kinase C and Exo1 (14-3-3 protein) and its relevance to exocytosis in permeabilized adrenal chromaffin cells. Biochem J. 1992 Sep 15;286(Pt 3):807–811. doi: 10.1042/bj2860807. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morgan A., Roth D., Martin H., Aitken A., Burgoyne R. D. Identification of cytosolic protein regulators of exocytosis. Biochem Soc Trans. 1993 May;21(2):401–405. doi: 10.1042/bst0210401. [DOI] [PubMed] [Google Scholar]
- Nielsen P. J. Primary structure of a human protein kinase regulator protein. Biochim Biophys Acta. 1991 Mar 26;1088(3):425–428. doi: 10.1016/0167-4781(91)90136-a. [DOI] [PubMed] [Google Scholar]
- Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
- Parker P. J., Kour G., Marais R. M., Mitchell F., Pears C., Schaap D., Stabel S., Webster C. Protein kinase C--a family affair. Mol Cell Endocrinol. 1989 Aug;65(1-2):1–11. doi: 10.1016/0303-7207(89)90159-7. [DOI] [PubMed] [Google Scholar]
- Parker P. J., Stabel S., Waterfield M. D. Purification to homogeneity of protein kinase C from bovine brain--identity with the phorbol ester receptor. EMBO J. 1984 May;3(5):953–959. doi: 10.1002/j.1460-2075.1984.tb01913.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Prasad G. L., Valverius E. M., McDuffie E., Cooper H. L. Complementary DNA cloning of a novel epithelial cell marker protein, HME1, that may be down-regulated in neoplastic mammary cells. Cell Growth Differ. 1992 Aug;3(8):507–513. [PubMed] [Google Scholar]
- Schlaepfer D. D., Jones J., Haigler H. T. Inhibition of protein kinase C by annexin V. Biochemistry. 1992 Feb 18;31(6):1886–1891. doi: 10.1021/bi00121a043. [DOI] [PubMed] [Google Scholar]
- Schwantke N., Le Peuch C. J. A protein kinase C inhibitory activity is present in rat brain homogenate. FEBS Lett. 1984 Nov 5;177(1):36–40. doi: 10.1016/0014-5793(84)80976-x. [DOI] [PubMed] [Google Scholar]
- Sutherland C., Alterio J., Campbell D. G., Le Bourdellès B., Mallet J., Haavik J., Cohen P. Phosphorylation and activation of human tyrosine hydroxylase in vitro by mitogen-activated protein (MAP) kinase and MAP-kinase-activated kinases 1 and 2. Eur J Biochem. 1993 Oct 15;217(2):715–722. doi: 10.1111/j.1432-1033.1993.tb18297.x. [DOI] [PubMed] [Google Scholar]
- Swanson K. D., Ganguly R. Characterization of a Drosophila melanogaster gene similar to the mammalian genes encoding the tyrosine/tryptophan hydroxylase activator and protein kinase C inhibitor proteins. Gene. 1992 Apr 15;113(2):183–190. doi: 10.1016/0378-1119(92)90394-5. [DOI] [PubMed] [Google Scholar]
- Toker A., Ellis C. A., Sellers L. A., Aitken A. Protein kinase C inhibitor proteins. Purification from sheep brain and sequence similarity to lipocortins and 14-3-3 protein. Eur J Biochem. 1990 Jul 31;191(2):421–429. doi: 10.1111/j.1432-1033.1990.tb19138.x. [DOI] [PubMed] [Google Scholar]
- Toker A., Sellers L. A., Amess B., Patel Y., Harris A., Aitken A. Multiple isoforms of a protein kinase C inhibitor (KCIP-1/14-3-3) from sheep brain. Amino acid sequence of phosphorylated forms. Eur J Biochem. 1992 Jun 1;206(2):453–461. doi: 10.1111/j.1432-1033.1992.tb16946.x. [DOI] [PubMed] [Google Scholar]
- Wu Y. N., Vu N. D., Wagner P. D. Anti-(14-3-3 protein) antibody inhibits stimulation of noradrenaline (norepinephrine) secretion by chromaffin-cell cytosolic proteins. Biochem J. 1992 Aug 1;285(Pt 3):697–700. doi: 10.1042/bj2850697. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yamauchi T., Nakata H., Fujisawa H. A new activator protein that activates tryptophan 5-monooxygenase and tyrosine 3-monooxygenase in the presence of Ca2+-, calmodulin-dependent protein kinase. Purification and characterization. J Biol Chem. 1981 Jun 10;256(11):5404–5409. [PubMed] [Google Scholar]
- Zupan L. A., Steffens D. L., Berry C. A., Landt M., Gross R. W. Cloning and expression of a human 14-3-3 protein mediating phospholipolysis. Identification of an arachidonoyl-enzyme intermediate during catalysis. J Biol Chem. 1992 May 5;267(13):8707–8710. [PubMed] [Google Scholar]
- van Heusden G. P., Wenzel T. J., Lagendijk E. L., de Steensma H. Y., van den Berg J. A. Characterization of the yeast BMH1 gene encoding a putative protein homologous to mammalian protein kinase II activators and protein kinase C inhibitors. FEBS Lett. 1992 May 11;302(2):145–150. doi: 10.1016/0014-5793(92)80426-h. [DOI] [PubMed] [Google Scholar]