The recognition of posttranslational modifications by modular protein domains is a fundamental determinant of selectivity in signaling pathways. In particular tyrosine (Tyr) phosphorylation pathways are regulated by a large number of different, modular phosphotyrosine (pTyr) recognition domains such as SH2 and PTB domains that recognize pTyr and coordinate signaling events downstream of kinases. While in eukaryotes, several pTyr recognition domains have independently evolved and in humans, for example, there are more pTyr recognition domains than Tyr kinases, no pTyr recognition domains have been identified in bacteria. Yet, pTyr reader domains evolved repeatedly, are highly versatile, are highly integrated parts of phosphorylation pathways, and are nearly ubiquitous except in bacteria. Given the large networks of Tyr phosphorylation in bacteria, it appears likely that bacteria also evolved pTyr recognition domains that remain to be discovered. Here, we will test this idea by identifying pTyr-binding proteins in Mtb.

Public Health Relevance

Phosphosignaling pathways mediate adaptation of microorganisms to changing environments. Usually, these pathways consist of kinases that add a phosphate group to protein, phosphatases that remove the phosphate, and phosphorecognition domains that recognize the modified protein. In bacteria, these phosphorecognition domains for phosphorylation of protein on tyrosine residues have not been identified. Here, we aim to identify these important components of signaling pathways in Mycobacterium tuberculosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Research Grants (R03)
Project #
5R03AI137599-03
Application #
9640417
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Mendez, Susana
Project Start
2018-02-06
Project End
2021-01-31
Budget Start
2019-02-01
Budget End
2021-01-31
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Seattle Children's Hospital
Department
Type
DUNS #
048682157
City
Seattle
State
WA
Country
United States
Zip Code
98105