Overview of Protein Microarrays

F.X. Reymond Sutandy1, Jiang Qian2, Chien‐Sheng Chen1, Heng Zhu3

1 Graduate Institute of Systems Biology and Bioinformatics, National Central University, Jhongli, Taiwan, 2 The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland, 3 High‐Throughput Biology Center, Johns Hopkins School of Medicine, Baltimore, Maryland
Publication Name:  Current Protocols in Protein Science
Unit Number:  Unit 27.1
DOI:  10.1002/0471140864.ps2701s72
Online Posting Date:  April, 2013
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library

Abstract

Protein microarray technology is an emerging field that provides a versatile platform for the characterization of hundreds of thousands of proteins in a highly parallel and high‐throughput manner. Protein microarrays are composed of two major classes: analytical and functional. In addition, tissue or cell lysates can also be fractionated and spotted on a slide to form a reverse‐phase protein microarray. Applications of protein microarrays, especially functional protein microarrays, have flourished over the past decade as the fabrication technology has matured. In this unit, advances in protein microarray technologies are reviewed, and then a series of examples are presented to illustrate the applications of analytical and functional protein microarrays in both basic and clinical research. Relevant areas of research include the detection of various binding properties of proteins, the study of protein post‐translational modifications, the analysis of host‐microbe interactions, profiling antibody specificity, and the identification of biomarkers in autoimmune diseases. Curr. Protoc. Protein Sci. 72:27.1.1‐27.1.16. © 2013 by John Wiley & Sons, Inc.

Keywords: protein microarrays; PTM; biomarker; network; systems biology

     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Table of Contents

  • Introduction
  • Types of Protein Microarrays
  • Fabrication of Protein Microarrays
  • Detection
  • Applications in Basic Research
  • Applications in Clinical Research
  • Future Prospects
  • Acknowledgements
  • Literature Cited
  • Figures
  • Tables
     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Materials

GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Figures

Videos

Literature Cited

Literature Cited
   Angenendt, P., Kreutzberger, J., Glökler, J., and Hoheisel, J.D. 2006. Generation of high density protein microarrays by cell‐free in situ expression of unpurified PCR products. Mol. Cell. Proteom. 5:1658‐1666.
   Brass, A.L., Huang, I.C., Benita, Y., John, S.P., Krishnan, M.N., Feeley, E.M., Ryan, B.J., Weyer, J.L., van der Weyden, L., Fikrig, E., Adams, D.J., Xavier, R.J., Farzan, M., and Elledge, S.J. 2009. The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell 139:1243‐1254.
   Brichta, J., Hnilova, M., and Viskovic, T. 2005. Generation of hapten‐specific recombinant antibodies: Antibody phage display technology: A review. Vet. Med. 50:231‐252.
   Carmen, S. and Jermutus, L. 2002. Concepts in antibody phage display. Brief. Funct. Genomic Proteomic 1:189‐203.
   Chao, G., Lau, W.L., Hackel, B.J., Sazinsky, S.L., Lippow, S.M., and Wittrup, K.D. 2006. Isolating and engineering human antibodies using yeast surface display. Nat. Protocols 1:755‐768.
   Charboneau, L., Tory, H., Chen, T., Winters, M., Petricoin, E.F. III, Liotta, L.A., and Paweletz, C.P. 2002. Utility of reverse phase protein arrays: Applications to signalling pathways and human body arrays. Brief. Funct. Genom. Proteom. 1:305‐315.
   Chen, C.‐S. and Zhu, H. 2006. Protein microarrays. BioTechniques 40:423‐429.
   Chen, C.‐S., Tao, S.‐C., and Zhu, H. 2008. Protein microarray technologies. In Proteomics (Methods Express Series; C.D. O'Connor and B.D. Hames, eds.) pp. 183‐205. Scion Publishing, Bloxham, U.K.
   Chen, C.‐S., Korobkova, E., Chen, H., Zhu, J., Jian, X., Tao, S.‐C., He, C., and Zhu, H. 2008. A proteome chip approach reveals new DNA damage recognition activities in Escherichia coli. Nat. Methods 5:69‐74.
   Chen, C.‐S., Sullivan, S., Anderson, T., Tan, A.C., Alex, P.J., Brant, S.R., Cuffari, C., Bayless, T.M., Talor, M.V., Burek, C.L., Wang, H., Li, R., Datta, L.W., Wu, Y., Winslow, R.L., Zhu, H., and Li, X. 2009. Identification of novel serological biomarkers for inflammatory bowel disease using Escherichia coli proteome chip. Mol. Cell. Proteom. 8:1765‐1776.
   Chen, F., Lu, H., Chen, Z., Zhao, T., and Yang, G. 2001. Optical real‐time monitoring of the laser molecular‐beam epitaxial growth of perovskite oxide thin films by an oblique‐incidence reflectance‐difference technique. J. Opt. Soc. Am. B 18:1031‐1035.
   Ciaccio, M.F., Wagner, J.P., Chuu, C.‐P., Lauffenburger, D.A., and Jones, R.B. 2010. Systems analysis of EGF receptor signaling dynamics with microwestern arrays. Nat. Methods 7:148‐155.
   Czajkowski, M. and Kretowski, M.K. 2011. Top scoring pair decision tree for gene expression data analysis. In Software Tools and Algorithms for Biological Systems (H.R. Arabnia and Q.‐N. Tran, eds.) pp. 27‐35. Springer Science+Business Media, New York.
   Doolan, D.L., Mu, Y., Unal, B., Sundaresh, S., Hirst, S., Valdez, C., Randall, A., Molina, D., Liang, X., Freilich, D.A., Oloo, J.A., Blair, P.L., Aguiar, J.C., Baldi, P., Davies, D.H., and Felgner, P.L. 2008. Profiling humoral immune responses to P. falciparum infection with protein microarrays. Proteomics 8:4680‐4694.
   Ekins, R.P. 1989. Multi‐analyte immunoassay. J. Pharm. Biomed. Anal. 7:155‐168.
   Espina, V., Wulfkuhle, J.D., Calvert, V.S., Petricoin, E.F. III, and Liotta, L.A. 2007. Reverse phase protein microarrays for monitoring biological responses. In Cancer Genomics and Proteomics: Methods and Protocols (P. Fisher, ed.) pp. 321‐336. Humana Press, Totowa, N.J.
   Evans‐Nguyen, K.M., Tao, S.‐C., Zhu, H., and Cotter, R.J. 2008. Protein arrays on patterned porous gold substrates interrogated with mass spectrometry: Detection of peptides in plasma. Anal. Chem. 80:1448‐1458.
   Foster, M.W., Forrester, M.T., and Stamler, J.S. 2009. A protein microarray‐based analysis of S‐nitrosylation. Proc. Natl. Acad. Sci. U.S.A. 106:18948‐18953.
   Gonzalez, R.M., Zhang, Q., Zangar, R.C., Smith, R.D., and Metz, T.O. 2011. Development of a fibrinogen‐specific sandwich enzyme‐linked immunosorbent assay microarray assay for distinguishing between blood plasma and serum samples. Anal. Biochem. 414:99‐102.
   Guo, A. and Zhu, X.‐Y. 2006. The critical role of surface chemistry in protein microarrays. In Functional Protein Microarrays in Drug Discovery (P.F. Predki, ed.) pp. 53‐72. CRC Press, Boca Raton, Fla.
   Gygi, S.P., Rochon, Y., Franza, B.R., and Aebersold, R. 1999. Correlation between protein and mRNA abundance in yeast. Mol. Cell. Biol. 19:1720‐1730.
   Haab, B.B. 2005. Antibody arrays in cancer research. Mol. Cell. Proteom. 4:377‐383.
   Hall, D.A., Ptacek, J., and Snyder, M. 2007. Protein microarray technology. Mech. Ageing Devel. 128:161‐167.
   Hall, D.A., Zhu, H., Zhu, X., Royce, T., Gerstein, M., and Snyder, M. 2004. Regulation of gene expression by a metabolic enzyme. Science 306:482‐484.
   Ho, S.‐W., Jona, G., Chen, C.T.L., Johnston, M., and Snyder, M. 2006. Linking DNA‐binding proteins to their recognition sequences by using protein microarrays. Proc. Natl. Acad. Sci. U.S.A. 103:9940‐9945.
   Ho, Y.‐H., Sung, T.‐C., and Chen, C.‐S. 2011. Lactoferricin B inhibits the phosphorylation of the two‐component system response regulators BasR and CreB. Mol. Cell. Proteom. 11:M111.014720.
   Hsu, K.‐L., Pilobello, K.T., and Mahal, L.K. 2006. Analyzing the dynamic bacterial glycome with a lectin microarray approach. Nat. Chem. Biol. 2:153‐157.
   Hu, S., Li, Y., Liu, G., Song, Q., Wang, L., Han, Y., Zhang, Y., Song, Y., Yao, X., Tao, Y., Zeng, H., Yang, H., Wang, J., Zhu, H., Chen, Z.‐N., and Wu, L. 2007. A protein chip approach for high‐throughput antigen identification and characterization. Proteomics 7:2151‐2161.
   Hu, S., Xie, Z., Onishi, A., Yu, X., Jiang, L., Lin, J., Rho, H.‐s., Woodard, C., Wang, H., and Jeong, J.‐S. 2009. Profiling the human protein‐DNA interactome reveals ERK2 as a transcriptional repressor of interferon signaling. Cell 139:610‐622.
   Huang, J., Zhu, H., Haggarty, S.J., Spring, D.R., Hwang, H., Jin, F., Snyder, M., and Schreiber, S.L. 2004. Finding new components of the target of rapamycin (TOR) signaling network through chemical genetics and proteome chips. Proc. Natl. Acad. Sci. U.S.A. 101:16594‐16599.
   Irving, R.A., Coia, G., Roberts, A., Nuttall, S.D., and Hudson, P.J. 2001. Ribosome display and affinity maturation: from antibodies to single V‐domains and steps towards cancer therapeutics. J. Immunol. Meth. 248:31‐45.
   Jeong, J.S., Jiang, L., Albino, E., Marrero, J., Rho, H.S., Hu, J., Hu, S., Vera, C., Bayron‐Poueymiroy, D., Rivera‐Pacheco, Z.A., Ramos, L., Torres‐Castro, C., Qian, J., Bonaventura, J., Boeke, J.D., Yap, W.Y., Pino, I., Eichinger, D.J., Zhu, H., and Blackshaw, S. 2012. Rapid identification of monospecific monoclonal antibodies using a human proteome microarray. Mol. Cell. Proteom. 11:O111.016253.
   Jones, R.B., Gordus, A., Krall, J.A., and MacBeath, G. 2006. A quantitative protein interaction network for the ErbB receptors using protein microarrays. Nature 439:168‐174.
   Karlas, A., Machuy, N., Shin, Y., Pleissner, K.‐P., Artarini, A., Heuer, D., Becker, D., Khalil, H., Ogilvie, L.A., Hess, S., Maürer, A.P., Müller, E., Wolff, T., Rudel, T., and Meyer, T.F. 2010. Genome‐wide RNAi screen identifies human host factors crucial for influenza virus replication. Nature 463:818‐822.
   Knappik, A. and Brundiers, R., 2009. Recombinant antibody expression and purification. In The Protein Protocols Handbook, 3rd ed. (J.M. Walker, ed) pp. 1929‐1943. Humana Press, New York.
   Knezevic, V., Leethanakul, C., Bichsel, V.E., Worth, J.M., Prabhu, V.V., Gutkind, J.S., Liotta, L.A., Munson, P.J., Petricoin, E.F. III, and Krizman, D.B. 2001. Proteomic profiling of the cancer microenvironment by antibody arrays. Proteomics 1:1271‐1278.
   Kopf, E. and Zharhary, D. 2007. Antibody arrays—An emerging tool in cancer proteomics. Int. J. Biochem. Cell Biol. 39:1305‐1317.
   Krogan, N.J., Cagney, G., Yu, H., Zhong, G., Guo, X., Ignatchenko, A., Li, J., Pu, S., Datta, N., Tikuisis, A.P., Punna, T., Peregrín‐Alvarez, J.M., Shales, M., Zhang, X., Davey, M., Robinson, M.D., Paccanaro, A., Bray, J.E., Sheung, A., Beattie, B., Richards, D.P., Canadien, V., Lalev, A., Mena, F., Wong, P., Starostine, A., Canete, M.M., Vlasblom, J., Wu, S., Orsi, C., Collins, S.R., Chandran, S., Haw, R., Rilstone, J.J., Gandi, K., Thompson, N.J., Musso, G., St Onge, P., Ghanny, S., Lam, M.H.Y., Butland, G., Altaf‐Ul, A.M., Kanaya, S., Shilatifard, A., O'Shea, E., Weissman, J.S., Ingles, C.J., Hughes, T.R., Parkinson, J., Gerstein, M., Wodak, S.J., Emili, A., and Greenblatt, J.F. 2006. Global landscape of protein complexes in the yeast Saccharomyces cerevisiae. Nature 440:637‐643.
   Kung, L.A., Tao, S.‐C., Qian, J., Smith, M.G., Snyder, M., and Zhu, H. 2009. Global analysis of the glycoproteome in Saccharomyces cerevisiae reveals new roles for protein glycosylation in eukaryotes. Mol Syst Biol 5:308.
   Landry, J.P., Sun, Y.S., Guo, X.W., and Zhu, X.D. 2008. Protein reactions with surface‐bound molecular targets detected by oblique‐incidence reflectivity difference microscopes. Appl. Opt. 47:3275‐3288.
   Li, R., Zhu, J., Xie, Z., Liao, G., Liu, J., Chen, M.‐R., Hu, S., Woodard, C., Lin, J., Taverna, S. D., Desai, P., Ambinder, R. F., Hayward, G. S., Qian, J., Zhu, H., and Hayward, S.D. 2011. Conserved herpesvirus kinases target the DNA damage response pathway and TIP60 histone acetyltransferase to promote virus replication. Cell Host Microbe 10:390‐400.
   Liang, L., Tan, X., Juarez, S., Villaverde, H., Pablo, J., Nakajima‐Sasaki, R., Gotuzzo, E., Saito, M., Hermanson, G., Molina, D., Felgner, S., Morrow, W.J.W., Liang, X., Gilman, R.H., Davies, D.H., Tsolis, R.M., Vinetz, J.M., and Felgner, P.L. 2011. Systems biology approach predicts antibody signature associated with Brucella melitensis infection in humans. J. Proteome Res. 10:4813‐4824.
   Lin, Y.‐Y., Lu, J.‐Y., Zhang, J., Walter, W., Dang, W., Wan, J., Tao, S.‐C., Qian, J., Zhao, Y., Boeke, J.D., Berger, S.L., and Zhu, H. 2009. Protein acetylation microarray reveals that NuA4 controls key metabolic target regulating gluconeogenesis. Cell 136:1073‐1084.
   Lu, J.‐Y., Lin, Y.‐Y., Qian, J., Tao, S.‐C., Zhu, J., Pickart, C., and Zhu, H. 2008. Functional dissection of a HECT ubiquitin E3 Ligase. Mol. Cell. Proteom. 7:35‐45.
   Lu, J.‐Y., Lin, Y.‐Y., Sheu, J.‐C., Wu, J.‐T., Lee, F.‐J., Chen, Y., Lin, M.‐I., Chiang, F.‐T., Tai, T.‐Y., Berger, S.L., Zhao, Y., Tsai, K.‐S., Zhu, H., Chuang, L.‐M., and Boeke, J.D. 2011. Acetylation of yeast AMPK controls intrinsic aging independently of caloric restriction. Cell 146:969‐979.
   Luevano, M., Bernard, H.‐U., Barrera‐Saldaña, H.A., Trevino, V., Garcia‐Carranca, A., Villa, L.L., Monk, B.J., Tan, X., Davies, D.H., Felgner, P.L., and Kalantari, M. 2010. High‐throughput profiling of the humoral immune responses against thirteen human papillomavirus types by proteome microarrays. Virology 405:31‐40.
   MacBeath, G. and Schreiber, S.L. 2000. Printing proteins as microarrays for high‐throughput function determination. Science 289:1760‐1763.
   Paweletz, C.P., Charboneau, L., Bichsel, V.E., Simone, N.L., Chen, T., Gillespie, J.W., Emmert‐Buck, M.R., Roth, M.J., Petricoin, E.F. III, and Liotta, L.A. 2001. Reverse phase protein microarrays which capture disease progression show activation of pro‐survival pathways at the cancer invasion front. Oncogene 20:1981‐1989.
   Piehler, J., Brecht, A., Gauglitz, G., Zerlin, M., Maul, C., Thiericke, R., and Grabley, S. 1997. Label‐free monitoring of DNA‐ligand interactions. Anal. Biochem. 249:94‐102.
   Pilobello, K.T., Slawek, D.E., and Mahal, L.K. 2007. A ratiometric lectin microarray approach to analysis of the dynamic mammalian glycome. Proc. Natl. Acad. Sci. U.S.A. 104:11534‐11539.
   Poetz, O., Schwenk, J.M., Kramer, S., Stoll, D., Templin, M.F., and Joos, T.O. 2005. Protein microarrays: Catching the proteome. Mech. Ageing Devel. 126:161‐170.
   Popescu, S.C., Popescu, G.V., Bachan, S., Zhang, Z., Seay, M., Gerstein, M., Snyder, M., and Dinesh‐Kumar, S.P. 2007. Differential binding of calmodulin‐related proteins to their targets revealed through high‐density Arabidopsis protein microarrays. Proc. Natl. Acad. Sci. U.S.A. 104:4730‐4735.
   Ptacek, J., Devgan, G., Michaud, G., Zhu, H., Zhu, X., Fasolo, J., Guo, H., Jona, G., Breitkreutz, A., Sopko, R., McCartney, R.R., Schmidt, M.C., Rachidi, N., Lee, S.‐J., Mah, A.S., Meng, L., Stark, M.J.R., Stern, D.F., De Virgilio, C., Tyers, M., Andrews, B., Gerstein, M., Schweitzer, B., Predki, P.F., and Snyder, M. 2005. Global analysis of protein phosphorylation in yeast. Nature 438:679‐684.
   Schnack, C., Hengerer, B., and Gillardon, F. 2008. Identification of novel substrates for Cdk5 and new targets for Cdk5 inhibitors using high‐density protein microarrays. Proteomics 8:1980‐1986.
   Schweitzer, B., Roberts, S., Grimwade, B., Shao, W., Wang, M., Fu, Q., Shu, Q., Laroche, I., Zhou, Z., Tchernev, V.T., Christiansen, J., Velleca, M., and Kingsmore, S.F. 2002. Multiplexed protein profiling on microarrays by rolling‐circle amplification. Nat. Biotech. 20:359‐365.
   Shapira, S.D., Gat‐Viks, I., Shum, B.O.V., Dricot, A., de Grace, M.M., Wu, L., Gupta, P.B., Hao, T., Silver, S.J., Root, D.E., Hill, D.E., Regev, A., and Hacohen, N. 2009. A physical and regulatory map of host‐influenza interactions reveals pathways in H1N1 infection. Cell 139:1255‐1267.
   Song, Q., Liu, G., Hu, S., Zhang, Y., Tao, Y., Han, Y., Zeng, H., Huang, W., Li, F., Chen, P., Zhu, J., Hu, C., Zhang, S., Li, Y., Zhu, H., and Wu, L. 2010. Novel autoimmune hepatitis‐specific autoantigens identified using protein microarray technology. J. Proteome Res. 9:30‐39.
   Tabata, N., Sakuma, Y., Honda, Y., Doi, N., Takashima, H., Miyamoto‐Sato, E., and Yanagawa, H. 2009. Rapid antibody selection by mRNA display on a microfluidic chip. Nucleic Acid Res. 37:e64.
   Talapatra, A., Rouse, R., and Hardiman, G. 2002. Protein microarrays: Challenges and promises. Pharmacogenomics 3:527‐536.
   Tao, S.‐C., Li, Y., Zhou, J., Qian, J., Schnaar, R.L., Zhang, Y., Goldstein, I.J., Zhu, H., and Schneck, J.P. 2008. Lectin microarrays identify cell‐specific and functionally significant cell surface glycan markers. Glycobiology 18:761‐769.
   Tao, S.‐C. and Zhu, H. 2006. Protein chip fabrication by capture of nascent polypeptides. Nat. Biotechnol. 24:1253‐1254.
   Tarrant, M.K., Rho, H.‐S., Xie, Z., Jiang, Y.L., Gross, C., Culhane, J.C., Yan, G., Qian, J., Ichikawa, Y., Matsuoka, T., Zachara, N., Etzkorn, F.A., Hart, G.W., Jeong, J.S., Blackshaw, S., Zhu, H., and Cole, P.A. 2012. Regulation of cK2 by phosphorylation and o‐glcnacylation revealed by semisynthesis. Nat. Chem. Biol. 8:262‐269.
   Thao, S., Chen, C.‐S., Zhu, H., and Escalante‐Semerena, J.C. 2010. Nɛ‐lysine acetylation of a bacterial transcription factor inhibits its DNA‐binding activity. PLoS One 5:e15123.
   Thiel, A.J., Frutos, A.G., Jordan, C.E., Corn, R.M., and Smith, L.M. 1997. In situ surface plasmon resonance imaging detection of DNA hybridization to oligonucleotide arrays on gold surfaces. Anal. Chem. 69:4948‐4956.
   Tu, Y.‐H., Ho, Y.‐H., Chuang, Y.‐C., Chen, P.‐C., and Chen, C.‐S. 2011. Identification of Lactoferricin B intracellular targets using an Escherichia coli proteome chip. PLoS One 6:e28197.
   Varnum, S.M., Woodbury, R.L., and Zangar, R.C., 2004. A protein microarray ELISA for screening biological fluids. In Protein Arrays: Methods and Protocols (E.T. Fung, ed.) pp. 161‐172. Humana Press, Totowa, N.J.
   Vidal, M., Brachmann, R.K., Fattaey, A., Harlow, E., and Boeke, J.D. 1996. Reverse two‐hybrid and one‐hybrid systems to detect dissociation of protein‐protein and DNA‐protein interactions. Proc. Natl. Acad. Sci. U.S.A. 93:10315‐10320.
   Vigil, A., Chen, C., Jain, A., Nakajima‐Sasaki, R., Jasinskas, A., Pablo, J., Hendrix, L.R., Samuel, J.E., and Felgner, P.L. 2011. Profiling the humoral immune response of acute and chronic Q fever by protein microarray. Mol. Cell. Proteom. 10:M110.006304.
   Wang, Z.H. and Jin, G. 2003. A label‐free multisensing immunosensor based on imaging ellipsometry. Anal. Chem. 75:6119‐6123.
   Xie, Z., Hu, S., Blackshaw, S., Zhu, H., and Qian, J. 2010. hPDI: A database of experimental human protein‐DNA interactions. Bioinformatics 26:287‐289.
   Yu, X., Xu, D., and Cheng, Q. 2006. Label‐free detection methods for protein microarrays. Proteomics 6:5493‐5503.
   Zhu, H. and Snyder, M. 2001. Protein arrays and microarrays. Curr. Opin. Chem. Biol. 5:40‐45.
   Zhu, H., Klemic, J.F., Chang, S., Bertone, P., Casamayor, A., Klemic, K.G., Smith, D., Gerstein, M., Reed, M.A., and Snyder, M. 2000. Analysis of yeast protein kinases using protein chips. Nat. Genet. 26:283‐289.
   Zhu, H., Bilgin, M., Bangham, R., Hall, D., Casamayor, A., Bertone, P., Lan, N., Jansen, R., Bidlingmaier, S., Houfek, T., Mitchell, T., Miller, P., Dean, R.A., Gerstein, M., and Snyder, M. 2001. Global analysis of protein activities using proteome chips. Science 293:2101‐2105.
   Zhu, H., Hu, S., Jona, G., Zhu, X., Kreiswirth, N., Willey, B.M., Mazzulli, T., Liu, G., Song, Q., Chen, P., Cameron, M., Tyler, A., Wang, J., Wen, J., Chen, W., Compton, S., and Snyder, M. 2006. Severe acute respiratory syndrome diagnostics using a coronavirus protein microarray. Proc. Natl. Acad. Sci. U.S.A. 103:4011‐4016.
   Zhu, J., Gopinath, K., Murali, A., Yi, G., Hayward, S.D., Zhu, H., and Kao, C. 2007. RNA‐binding proteins that inhibit RNA virus infection. Proc. Natl. Acad. Sci. U.S.A. 104:3129‐3134.
   Zhu, J., Liao, G., Shan, L., Zhang, J., Chen, M.‐R., Hayward, G.S., Hayward, S.D., Desai, P., and Zhu, H. 2009. Protein array identification of substrates of the Epstein‐Barr virus protein kinase BGLF4. J. Virol. 83:5219‐5231.
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library