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Outline

Title
Abstract
Scope of the Thesis
Maldi-Tof/Tof Mass Spec Analysis
Introduction
Materials and Methods
Sequence Logos and Database Searching
Results
Discussion
Conclusion
References
All Topics
Biology
Biochemistry

Differentially activating the oncogenic kinase Akt1

Profile image of Nileeka BalasuriyaNileeka Balasuriya

2019

https://doi.org/10.1080/15476286.15472019.11608754
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204 pages

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Abstract

Kunkel conducted the FRET based cell assays. X. Liu and K.K. Biggar performed the mass spec analysis. All other experiments were conducted by N. Balasuriya. Manuscript was written by N. balasuriya, M.T.

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  273. Gallay, N., Dos Santos, C., Cuzin, L., Bousquet, M., Simmonet Gouy, V., Chaussade, C., Attal, M., Payrastre, B., Demur, C., and Recher, C. (2009) The level of AKT phosphorylation on threonine 308 but not on serine 473 is associated with high-risk cytogenetics and predicts poor overall survival in acute myeloid leukaemia. Leukemia 23, 1029-1038
  274. Laity, J. H., Lee, B. M., and Wright, P. E. (2001) Zinc finger proteins: new insights into structural and functional diversity. Curr Opin Struct Biol 11, 39-46
  275. Katoh, T., Sakaguchi, Y., Miyauchi, K., Suzuki, T., Kashiwabara, S., Baba, T., and Suzuki, T. (2009) Selective stabilization of mammalian microRNAs by 3' adenylation mediated by the cytoplasmic poly(A) polymerase GLD-2. Genes Dev 23, 433-438
  276. Rissland, O. S., Mikulasova, A., and Norbury, C. J. (2007) Efficient RNA polyuridylation by noncanonical poly(A) polymerases. Mol Cell Biol 27, 3612-3624
  277. Bellacosa, A., Kumar, C. C., Di Cristofano, A., and Testa, J. R. (2005) Activation of AKT kinases in cancer: implications for therapeutic targeting. Adv Cancer Res 94, 29-86
  278. Freudlsperger, C., Horn, D., Weissfuss, S., Weichert, W., Weber, K. J., Saure, D., Sharma, S., Dyckhoff, G., Grabe, N., Plinkert, P., Hoffmann, J., Freier, K., and Hess, J. (2015) Phosphorylation of AKT(Ser473) serves as an independent prognostic marker for radiosensitivity in advanced head and neck squamous cell carcinoma. Int J Cancer 136, 2775-2785
  279. Manning, B. D., and Cantley, L. C. (2007) AKT/PKB signaling: navigating downstream. Cell 129, 1261-1274
  280. Hanada, M., Feng, J., and Hemmings, B. A. (2004) Structure, regulation and function of PKB/AKT--a major therapeutic target. Biochim Biophys Acta 1697, 3-16
  281. Manning, B. D., and Toker, A. (2017) AKT/PKB Signaling: Navigating the Network. Cell 169, 381-405
  282. Gallay, N., Dos Santos, C., Cuzin, L., Bousquet, M., Simmonet Gouy, V., Chaussade, C., Attal, M., Payrastre, B., Demur, C., and Recher, C. (2009) The level of AKT phosphorylation on threonine 308 but not on serine 473 is associated with high-risk cytogenetics and predicts poor overall survival in acute myeloid leukaemia. Leukemia 23, 1029-1038
  283. Balasuriya, N., Kunkel, M. T., Liu, X., Biggar, K. K., Li, S. S., Newton, A. C., and O'Donoghue, P. (2018) Genetic code expansion and live cell imaging reveal that Thr-308 phosphorylation is irreplaceable and sufficient for Akt1 activity. J Biol Chem 293, 10744-10756
  284. Dissmeyer, N., and Schnittger, A. (2011) Use of phospho-site substitutions to analyze the biological relevance of phosphorylation events in regulatory networks. Methods in molecular biology 779, 93-138
  285. Balasuriya, N., McKenna, M., Liu, X., Li, S. S. C., and O'Donoghue, P. (2018) Phosphorylation-Dependent Inhibition of Akt1. Genes (Basel) 9
  286. Barnett, S. F., Defeo-Jones, D., Fu, S., Hancock, P. J., Haskell, K. M., Jones, R. E., Kahana, J. A., Kral, A. M., Leander, K., Lee, L. L., Malinowski, J., McAvoy, E. M., Nahas, D. D., Robinson, R. G., and Huber, H. E. (2005) Identification and characterization of pleckstrin-homology-domain- dependent and isoenzyme-specific Akt inhibitors. Biochem J 385, 399-408
  287. Jacinto, E., Facchinetti, V., Liu, D., Soto, N., Wei, S., Jung, S. Y., Huang, Q., Qin, J., and Su, B. (2006) SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity. Cell 127, 125-137
  288. Chung, C., Balasuriya, N., Manni, E., Liu, X., Li, S.-C., O'Donoghue, P., and Heinemann, I. U. (2019) Gld2 activity is regulated by phosphorylation in the N-terminal domain. RNA Biol, DOI:10.1080/15476286.15472019.11608754
  289. Altomare, D. A., and Testa, J. R. (2005) Perturbations of the AKT signaling pathway in human cancer. Oncogene 24, 7455-7464
  290. Gonzalez, E., and McGraw, T. E. (2009) The Akt kinases: isoform specificity in metabolism and cancer. Cell Cycle 8, 2502-2508
  291. Bellacosa, A., Kumar, C. C., Di Cristofano, A., and Testa, J. R. (2005) Activation of AKT kinases in cancer: implications for therapeutic targeting. Adv Cancer Res 94, 29-86
  292. Nitulescu, G. M., Margina, D., Juzenas, P., Peng, Q., Olaru, O. T., Saloustros, E., Fenga, C., Spandidos, D., Libra, M., and Tsatsakis, A. M. (2016) Akt inhibitors in cancer treatment: The long journey from drug discovery to clinical use (Review). International journal of oncology 48, 869-885
  293. Tamura, K., Hashimoto, J., Tanabe, Y., Kodaira, M., Yonemori, K., Seto, T., Hirai, F., Arita, S., Toyokawa, G., Chen, L., Yamamoto, H., Kawata, T., Lindemann, J., and Esaki, T. (2016) Safety and tolerability of AZD5363 in Japanese patients with advanced solid tumors. Cancer chemotherapy and pharmacology 77, 787-795
  294. Curriculum Vitae Nileeka Balasuriya BSc, MSc Post-secondary education and degrees: University of Peradeniya, Peradeniya, Sri Lanka 2004-2008, BSc Dalhousie University, Halifax, Nova Scotia, Canada 2009-2011, MSc University of Western Ontario, London, Ontario, Canada 2014-2019, PhD Honours and Awards
  295. Canadian Cancer Society travel award (valued $2000): Awarded to attend the "protein kinases and protein phosphorylation" conference held in Cambridge, UK (August 6-11, 2017)
  296. Queen Elizabeth II Graduate Student Scholarship (valued $15000): Biochemistry Department, Schulich School of Medicine and Dentistry University of Western Ontario- 2015/2016
  297. Gold category award and cash prize: Canadian Student Health Research Forum 2016, Winnipeg, Manitoba
  298. Ontario Graduate Student Scholarship (valued $15000): Biochemistry Department, Schulich School of Medicine and Dentistry, University of Western Ontario-2017/2018
  299. Represented the student group from Schulic School of Medicine and Dentistry participated in the Canadian Student Health Research Forum 2016 which gathers the top 5% PhD students across the Canadian medical schools
  300. Schulich Graduate Scholarship (Valued $2000 per year) Biochemistry Department, Schulich School of Medicine and Dentistry, University of Western Ontario (2015-2017)
  301. International Union of Nutritional Sciences (IUNS) Travel Fund Agricultural Institute of Canada Foundation (AICF) -2010/11: Awarded to attend the Proceedings of the 7 th International Conference of Functional Foods for Prevention and Management of Metabolic Syndrome. Dallas, Texas, US. Dec. 2-4, 2010
  302. Entrance Scholarship (valued $5000): Faculty of Agriculture, Dalhousie University - 2009-2011
  303. Best Oral Presentation: Graduate Research Day, 2010
  304. Gold Medal: Best academic performance of the B.Sc. Food Science and Technology degree, University of Peredaniya, Sri Lanka (2004-2008)
  305. Gold Medal: Best performance in food quality control -B.Sc. Food Science and Technology degree, University of Peredaniya, Sri Lanka (2004-2008)
  306. Related Work Experience Teaching assistant: Biochemistry laboratory 3380G, Biochemistry Department, Western University (2015-2018)
  307. Graduate research assistant: Biochemistry Department (O'Donoghue laboratory) Western University (2014-2018)
  308. Chung, C., Balasuriya, N., Manni, E., Liu, X., Li, S.-C., O'Donoghue, P., and Heinemann, I. U. (2019) Gld2 activity is regulated by phosphorylation in the N-terminal domain. RNA Biol, DOI:10.1080/15476286.15472019.11608754
  309. Balasuriya, N., McKenna, M., Liu, X., Li, S. S. C., and O'Donoghue, P. Phosphorylation- dependent inhibition of Akt1. Genes (Basel) 2018 9(9), 450
  310. Balasuriya, N., Kunkel, M., Biggar, K., Li, S., Newton, A., O'Donoghue, P. 2018. Genetic code expansion and live cell imaging reveal that Thr308 phosphorylation is irreplaceble and sufficent for Akt1 activity. Journal of Biological Chemistry. 2018, 293, 10744-10756.
  311. Ejike, C. E. C. C., Collins, S. A., Balasuriya, N., Swanson, A.K., Mason, B., Udenigwe, C. C. Prospects of microalgae proteins in producing peptide-based functional foods for promoting cardiovascular health. Trends in Food Science and Technology. 2017, 59, 30- 36.
  312. Balasuriya, N., Rupasinghe, H. P. V., Sweeney, M., McCarron, S. and Gottschall-Pass, K. Antihypertensive effects of apple peel extract on spontaneously hypertensive rats. Pharmacologia. 2015, 6(8), 371-376.
  313. Balasuriya, N. and Rupasinghe, H. P. V. Antihypertensive properties of flavonoid rich apple peel extract. Food Chemistry. 2012, 135, (4) 2320-2325.
  314. Balasuriya, B.W.N. and Rupasinghe, H. P.V. Plant flavonoids as angiotensin converting enzyme inhibitors in regulation of hypertension. Functional Foods in Health Disease. 2011, 5, 172-188.
  315. Book Chapters: Rupasinghe, H. P. V., Balasuriya, N., Wang Y., Prevention of type 2 diabetes by polyphenols of fruits. In book Nutritional and Antioxidant Therapies: Treatments and Perspectives. 2017. DOI: 10.1007/978-3-319-67625-8_18. Abstracts of conferences attended: PhD International
  316. Functional characterization of differentially activated oncogenic kinase Akt1. Protein kinases and protein phosphorylation. Federation of American Societies of Experimental Biology. Cambridge, UK. August, 2017. (Poster presentation)
  317. Activating the oncogenic kinase Akt1 by genetically encoded phosphorylation. International Union of Molecular Biology and Biochemistry. Vancouver, BC. July, 2016. (Poster presentation)
  318. Differentially activated oncogenic kinase Akt1. London Health Research Day. London, ON. March, 2017. (Poster presentation)
  319. Reassignment of the genetic code using phosphoserine in synthesizing differentially activated Akt1. Canadian Student Health Research Forum. University of Manitoba, Winnipeg, June, 2016. (Poster presentation)
  320. Synthesis of differentially activated oncogenic kinase Akt1 by site-specific incorporation of phosphoserine. London Health Research Day. London, ON. March, 2016. (Poster presentation) Abstracts of conferences attended: MSc International
  321. Antihypertensive effects of apple peel extract (APE) on spontaneously hypertensive rats. Nileeka Balasuriya, H.P. Vasantha Rupasinghe, Marva Sweeney, Shelby McCarron and Katherine Gottschall-Pass. 17 th World Congress of Food Science. Montreal, Canada. August 17-21, 2014. (Poster presentation)
  322. Antihypertensive properties of fruit bioactives. Nileeka Balasuriya and Vasantha Rupasinghe. Proceedings of the Plant Canada Conference. St. Mary's University. Halifax, Canada. July 17 -21, 2011. (Oral presentation)
  323. Inhibition of angiotensin converting enzyme by wild berry extracts in vitro. Nileeka Balasuriya and Vasantha Rupasinghe. Proceedings of the 8 th Annual Conference of Natural Health Products Research Society -Joining Forces for a Healthier Tomorrow. Montreal, Canada. May 24 -27, 2011. (Oral presentation)
  324. Inhibition of angiotensin converting enzyme in vitro by apple skin extract, selected flavonoids and their metabolites. Nileeka Balasuriya and Vasantha Rupasinghe. Proceedings of the 7 th International Conference of Functional Foods for Prevention and Management of Metabolic Syndrome. Dallas, Texas, US. Dec. 2-4, 2010. (Oral presentation) Local
  325. Effects of flavonoid-rich apple peel extract on biomarkers of oxidative stress in spontaneously hypertensive rat kidneys. Iain McPhee, Nileeka Balasuriya, Shelby McCarron, H.P. Vasantha Rupasinghe, Marva Sweeney-Nixon and Katherine Gottschall- Pass. AUBC Conference. University of Prince Edward Island, 2014. (Poster presentation)

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