title: Mycobacterium tuberculosis supports protein tyrosine phosphorylation.
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.
authors.affiliation: Institute for Systems Biology, Seattle, WA 98109;
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kusebauch
authors.affiliation: Seattle Biomedical Research Institute, Seattle, WA 98109; andDepartment of Global Health, University of Washington, Seattle, WA, 98195.
authors.forename: Corrie
authors.initials: C
authors.lastname: Ortega
authors.affiliation: Seattle Biomedical Research Institute, Seattle, WA 98109; and.
authors.forename: Anja
authors.initials: A
authors.lastname: Ollodart
authors.affiliation: Institute for Systems Biology, Seattle, WA 98109;
authors.forename: Richard S
authors.initials: RS
authors.lastname: Rogers
authors.affiliation: Seattle Biomedical Research Institute, Seattle, WA 98109; andDepartment of Global Health, University of Washington, Seattle, WA, 98195.
authors.forename: David R
authors.initials: DR
authors.lastname: Sherman
authors.affiliation: Institute for Systems Biology, Seattle, WA 98109; robert.moritz@sytemsbiology.org christoph.grundner@seattlebiomed.org.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Moritz
authors.affiliation: 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.
authors.forename: Christoph
authors.initials: C
authors.lastname: Grundner
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000235:genetics; D010766:Phosphorylation / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; C475060:PknB protein, Mycobacterium tuberculosis; D017346:Protein Serine-Threonine Kinases