on 12-23-201408:34 AM - edited on 10-15-202111:35 AM by Closed Account
Kusebauch U, Ortega C, Ollodart A, Rogers RS, Sherman DR, Moritz RL, Grundner C. Proc Natl Acad Sci U S A. 2014 Jun 24;111(25):9265-70. doi: 10.1073/pnas.1323894111. Epub 2014 Jun 9. 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.