Serine/threonine phosphorylation in mycobacterium tuberculosis : identification of protein kinase B (PknB) substrates

Tuberculosis, caused by the intracellular pathogen Mycobacterium tuberculosis, is one of the most prevalent infectious diseases in our world today. In order to survive within the host the bacteria need to sense and respond to changes in the environment; however, signal transduction in this bacterium is poorly understood. PknB is a serine/threonine kinase essential for the in vitro survival of M. tuberculosis and therefore a potential drug target against the bacteria. It is the goal of the current study to elucidate downstream substrates of PknB. We have found that PknB shares in vitro substrates with another serine/threonine kinase, PknH, implying the potential complexity of the signaling pathways in the bacteria. We have also provided the first description of the coupling between serine/threonine kinases PknB and PknH with a two-component system response regulator DevR, and further proposed Ser/Thr phosphorylation as the negative regulator of DevR transcription activator activity based on LC-MS/MS analysis. Finally, we have identified a previously unknown phosphoprotein glyceraldehyde 3-phosphate dehydrogenase encoded by the ORF Rv1436, which demonstrates autophosphorylation activity and which phosphorylation is independent of PknB. Overall, the current study has contributed to advance our understanding of the signal transduction pathways and phosphoproteome in Mycobacterium tuberculosis.

Name thesis:degree_name

Master of Science - MSc

Level thesis:degree_level

master's

Discipline thesis:degree_discipline

Experimental Medicine

Grantor dc:publisher

University of British Columbia

Year dc:date

2008

Author dc:creator

• Lee, Guinevere Kwun Wing Queenie

Statement dc:rights

• Attribution-NonCommercial-NoDerivatives 4.0 International

Licence

• http://creativecommons.org/licenses/by-nc-nd/4.0/

Language dc:language

eng

Handle dc:identifier

http://hdl.handle.net/2429/693

OAI identifier oai:identifier

oai:circle.library.ubc.ca:2429/693