Abstract
We have developed a method to identify previously undetected histidine and aspartic acid phosphorylations in a human prostate cancer progression model. A phosphoproteome of our cell line model is presented, with correlation of modified protein expression between the three states of cancer: non-tumorigenic, tumorigenic, and metastatic cells. With the described interaction proteins potentially phosphorylated by NM23-H1, cellular responses to motility and conformational change stimuli would be achievable. We detect 20 novel histidine-phosphorylated (pHis) and 80 novel aspartic acid-phosphorylated (pAsp) proteins with diverse functions, such as metabolism, protein folding, and motility. Our data indicate that pHis and pAsp are much more prevalent than previously appreciated and may provide insight into the role of NM23-H1 and signaling events that are critical for metastasis. Using the described method for detecting histidine and aspartic acid phosphorylations and our prostate cancer progression cell system, the potential function of NM23-H1 in suppressing metastasis with a two-component regulation system is discussed.
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References
An R et al. Expressions of nucleoside diphosphate kinase (nm23) in tumor tissues are related with metastasis and length of survival of patients with hepatocellular carcinoma Biomed Environ Sci 23:267–272. doi:10.1016/S0895-3988(10)60062-1
Attwood PV, Piggott MJ, Zu XL, Besant PG (2007) Focus on phosphohistidine. Amino Acids 32:145–156. doi:10.1007/s00726-006-0443-6
Bailey TL, Elkan C (1994) Fitting a mixture model by expectation maximization to discover motifs in biopolymers Proceedings / International Conference on Intelligent Systems for Molecular Biology; ISMB International Conference on Intelligent Systems for Molecular Biology 2:28–36
Besant PG, Attwood PV (2000) Int J Biochem Cell Biol 32:243–253
Besant PG, Attwood PV (2005) Mammalian histidine kinases. Biochim Biophys Acta 1754:281–290. doi:10.1016/j.bbapap.2005.07.026
Besant PG, Attwood PV (2009) Detection and analysis of protein histidine phosphorylation. Mol Cell Biochem 329:93–106. doi:10.1007/s11010-009-0117-2
Ciesla J, Fraczyk T, Rode W (2011) Phosphorylation of basic amino acid residues in proteins: important but easily missed. Acta Biochim Pol 58:137–148
Conrads TP, Issaq HJ, Veenstra TD (2002) New tools for quantitative phosphoproteome analysis. Biochem Biophys Res Commun 290:885–890. doi:10.1006/bbrc.2001.6275
Cuello F et al (2003) Activation of heterotrimeric G proteins by a high energy phosphate transfer via nucleoside diphosphate kinase (NDPK) B and Gbeta subunits. Complex formation of NDPK B with Gbeta gamma dimers and phosphorylation of His-266 IN Gbeta. J Biol Chem 278:7220–7226. doi:10.1074/jbc.M210304200M210304200
Cunha GR, Lung B (1979) The importance of stroma in morphogenesis and functional activity of urogenital epithelium. In Vitro 15:50–71
Cunha GR, Hayward SW, Wang YZ, Ricke WA (2003) Role of the stromal microenvironment in carcinogenesis of the prostate. Int J Cancer 107:1–10. doi:10.1002/ijc.11335
Cunha GR et al (2004) Hormonal, cellular, and molecular regulation of normal and neoplastic prostatic development. J Steroid Biochem Mol Biol 92:221–236. doi:10.1016/j.jsbmb.2004.10.017
Ficarro SB et al (2002) Phosphoproteome analysis by mass spectrometry and its application to Saccharomyces cerevisiae. Nat Biotechnol 20:301–305. doi:10.1038/nbt0302-301
Filiz G, Adim S, Aytac B, Akar E, Vuruskan H Significance of nm23 immunoexpression in the prognosis of renal cell carcinoma J Int Med Res 38:620–624
Gounaris K, Thomas S, Najarro P, Selkirk ME (2001) Secreted variant of nucleoside diphosphate kinase from the intracellular parasitic nematode. Trichinella spiralis Infect Immu 69:3658–3662. doi:10.1128/IAI. 69.6.3658-3662.2001
Gullon S, Vicente RL, Mellado RP (2012) A novel two-component system involved in secretion stress response in Streptomyces lividans. PLoS One 7:e48987. doi:10.1371/journal.pone.0048987
Hartsough MT et al (2002) Nm23-H1 metastasis suppressor phosphorylation of kinase suppressor of Ras via a histidine protein kinase pathway. J bio chem 277:32389–32399. doi:10.1074/jbc.M203115200
Hippe HJ et al (2009) The interaction of nucleoside diphosphate kinase B with Gbetagamma dimers controls heterotrimeric G protein function. Proc Natl Acad Sci U S A 106:16269–16274
Hoch JA (2000) Two-component and phosphorelay signal transduction. Curr Opin Microbiol 3:165–170
Horak CE et al (2007) Nm23-H1 suppresses metastasis by inhibiting expression of the lysophosphatidic acid receptor EDG2. Cancer Res 67:11751–11759. doi:10.1158/0008-5472.CAN-07-3175
Hyyrylainen HL et al (2001) A novel two-component regulatory system in Bacillus subtilis for the survival of severe secretion stress. Mol Microbiol 41:1159–1172
Karin M, Ben-Neriah Y (2000) Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Annu Rev Immunol 18:621–663. doi:10.1146/annurev.immunol.18.1.621
Klumpp S, Krieglstein J (2009) Reversible phosphorylation of histidine residues in proteins from vertebrates. Sci Signal 2:13
Kroemer G, Marino G, Levine B (2010) Autophagy and the integrated stress response. Mol Cell 40:280–293. doi:10.1016/j.molcel.2010.09.023
Kuchma SL, Connolly JP, O’Toole GA (2005) A three-component regulatory system regulates biofilm maturation and type III secretion in Pseudomonas aeruginosa. J Bacteriol 187:1441–1454. doi:10.1128/JB.187.4.1441-1454.2005
Lapek JD Jr, Tombline G, Friedman AE (2011) Mass spectrometry detection of histidine phosphorylation on NM23-H1. J Proteome Res 10:751–755. doi:10.1021/pr100905m
Lapek JD Jr, McGrath JL, Ricke WA, Friedman AE (2012) LC/LC-MS/MS of an innovative prostate human epithelial cancer (PHEC) in vitro model system. J Chromatogr B Anal Technol Biomed Life Sci 893–894:34–42. doi:10.1016/j.jchromb.2012.02.029
Lee HY, Lee H (1999) Inhibitory activity of nm23-H1 on invasion and colonization of human prostate carcinoma cells is not mediated by its NDP kinase activity. Cancer Lett 145:93–99
Liu Q, Cobb JS, Johnson JL, Wang Q, Agar JN (2014) Performance comparisons of nano-LC systems, electrospray sources and LC-MS-MS platforms. J Chromatogr Sci 52:120–127. doi:10.1093/chromsci/bms255
Macek B, Mijakovic I (2011) Site-specific analysis of bacterial phosphoproteomes. Proteomics 11:3002–3011. doi:10.1002/pmic.201100012
Macek B, Gnad F, Soufi B, Kumar C, Olsen JV, Mijakovic I, Mann M (2008) Phosphoproteome analysis of E. coli reveals evolutionary conservation of bacterial Ser/Thr/Tyr phosphorylation. Mol Cell Proteomics 7:299–307. doi:10.1074/mcp. M700311-MCP200
Marshall JC, Lee JH, Steeg PS (2009) Clinical-translational strategies for the elevation of Nm23-H1 metastasis suppressor gene expression. Mol Cell Biochem 329:115–120. doi:10.1007/s11010-009-0116-3
Marshall JC et al (2012) Effect of inhibition of the lysophosphatidic acid receptor 1 on metastasis and metastatic dormancy in breast cancer. J Natl Cancer Inst 104:1306–1319. doi:10.1093/jnci/djs319
Miller MB, Bassler BL (2001) Quorum sensing in bacteria. Annu Rev Microbiol 55:165–199. doi:10.1146/annurev.micro.55.1.165
Ng WL, Bassler BL (2009) Bacterial quorum-sensing network architectures. Annu Rev Genet 43:197–222. doi:10.1146/annurev-genet-102108-134304
Pearson MA, Reczek D, Bretscher A, Karplus PA (2000) Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain. Cell 101:259–270
Perkins DN, Pappin DJ, Creasy DM, Cottrell JS (1999) Probability-based protein identification by searching sequence databases using mass spectrometry data. Electrophoresis 20:3551–3567. doi:10.1002/(SICI)1522-2683(19991201)20:18<3551::AID-ELPS3551>3.0.CO;2–2
Ricke WA, Ishii K, Ricke EA, Simko J, Wang Y, Hayward SW, Cunha GR (2006) Steroid hormones stimulate human prostate cancer progression and metastasis. Int J Cancer 118:2123–2131. doi:10.1002/ijc.21614
Roymans D, Willems R, Van Blockstaele DR, Slegers H (2002) Nucleoside diphosphate kinase (NDPK/NM23) and the waltz with multiple partners: possible consequences in tumor metastasis. Clin Exp Metastasis 19:465–476
Salerno M, Palmieri D, Bouadis A, Halverson D, Steeg PS (2005) Nm23-H1 metastasis suppressor expression level influences the binding properties, stability, and function of the kinase suppressor of Ras1 (KSR1) Erk scaffold in breast carcinoma cells. Mol Cell Biol 25:1379–1388. doi:10.1128/MCB. 25.4.1379-1388.2005
Schlessinger J (2000) Cell signaling by receptor tyrosine kinases. Cell 103:211–225
Shevchenko A, Tomas H, Havlis J, Olsen JV, Mann M (2006) In-gel digestion for mass spectrometric characterization of proteins and proteomes. Nat Protoc 1:2856–2860. doi:10.1038/nprot.2006.468
Smtih DL, Bruegger BB, Halpern RM, Smith RA (1973) New histone kinases in nuclei of rat tissues. Nature 246:103–104
Srivastava S et al (2006) Histidine phosphorylation of the potassium channel KCa3.1 by nucleoside diphosphate kinase B is required for activation of KCa3.1 and CD4 T cells. Mol Cell 24:665–675
Steeg PS, Bevilacqua G, Kopper L, Thorgeirsson UP, Talmadge JE, Liotta LA, Sobel ME (1988) Evidence for a novel gene associated with low tumor metastatic potential. J Natl Cancer Inst 80:200–204
Tao WA et al (2005) Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry. Nat Methods 2:591–598. doi:10.1038/nmeth776
Wagner PD, Vu ND (1995) Phosphorylation of ATP-citrate lyase by nucleoside diphosphate kinase. J Biol Chem 270:21758–21764
Wagner PD, Vu ND (2000) Histidine to aspartate phosphotransferase activity of nm23 proteins: phosphorylation of aldolase C on Asp-319. Biochem J 346(3):623–630
Westers H, Westers L, Darmon E, van Dijl JM, Quax WJ, Zanen G (2006) The CssRS two-component regulatory system controls a general secretion stress response in Bacillus subtilis. FEBS J 273:3816–3827. doi:10.1111/j.1742-4658.2006.05389.x
Wiener MC, Sachs JR, Deyanova EG, Yates NA (2004) Differential mass spectrometry: a label-free LC-MS method for finding significant differences in complex peptide and protein mixtures. Anal Chem 76:6085–6096. doi:10.1021/ac0493875
Acknowledgments
We thank William Ricke for the PHEC cell lines. AEF derived funding from NIH, 1 UL1 RR024160-1, National Institute of Environmental Health Sciences Training Grant ES07026 and Center Grant ES01247, and U of R start-up funds (AEF).
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The authors have no conflict of interest in this work.
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Lapek, J.D., Tombline, G., Kellersberger, K.A. et al. Evidence of histidine and aspartic acid phosphorylation in human prostate cancer cells. Naunyn-Schmiedeberg's Arch Pharmacol 388, 161–173 (2015). https://doi.org/10.1007/s00210-014-1063-4
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DOI: https://doi.org/10.1007/s00210-014-1063-4