Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2014 Jun 24;111(25):9265-70. doi: 10.1073/pnas.1323894111. Epub 2014 Jun 9.

Mycobacterium tuberculosis supports protein tyrosine phosphorylation.

Author information

1
Institute for Systems Biology, Seattle, WA 98109;
2
Seattle Biomedical Research Institute, Seattle, WA 98109; andDepartment of Global Health, University of Washington, Seattle, WA, 98195.
3
Seattle Biomedical Research Institute, Seattle, WA 98109; and.
4
Institute for Systems Biology, Seattle, WA 98109; robert.moritz@sytemsbiology.org christoph.grundner@seattlebiomed.org.
5
Seattle Biomedical Research Institute, Seattle, WA 98109; andDepartment of Global Health, University of Washington, Seattle, WA, 98195 robert.moritz@sytemsbiology.org christoph.grundner@seattlebiomed.org.

Abstract

Reversible protein phosphorylation determines growth and adaptive decisions in Mycobacterium tuberculosis (Mtb). At least 11 two-component systems and 11 Ser/Thr protein kinases (STPKs) mediate phosphorylation on Asp, His, Ser, and Thr. In contrast, protein phosphorylation on Tyr has not been described previously in Mtb. Here, using a combination of phospho-enrichment and highly sensitive mass spectrometry, we show extensive protein Tyr phosphorylation of diverse Mtb proteins, including STPKs. Several STPKs function as dual-specificity kinases that phosphorylate Tyr in cis and in trans, suggesting that dual-specificity kinases have a major role in bacterial phospho-signaling. Mutation of a phosphotyrosine site of the essential STPK PknB reduces its activity in vitro and in live Mtb, indicating that Tyr phosphorylation has a functional role in bacterial growth. These data identify a previously unrecognized phosphorylation system in a human pathogen that claims ∼ 1.4 million lives every year.

PMID:
24927537
PMCID:
PMC4078798
DOI:
10.1073/pnas.1323894111
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center