Extensive phosphorylation with overlapping specificity by Mycobacterium tuberculosis serine/threonine protein kinases.

Published

Journal Article

The Mycobacterium tuberculosis genome encodes 11 serine/threonine protein kinases (STPKs) that are structurally related to eukaryotic kinases. To gain insight into the role of Ser/Thr phosphorylation in this major global pathogen, we used a phosphoproteomic approach to carry out an extensive analysis of protein phosphorylation in M. tuberculosis. We identified more than 500 phosphorylation events in 301 proteins that are involved in a broad range of functions. Bioinformatic analysis of quantitative in vitro kinase assays on peptides containing a subset of these phosphorylation sites revealed a dominant motif shared by six of the M. tuberculosis STPKs. Kinase assays on a second set of peptides incorporating targeted substitutions surrounding the phosphoacceptor validated this motif and identified additional residues preferred by individual kinases. Our data provide insight into processes regulated by STPKs in M. tuberculosis and create a resource for understanding how specific phosphorylation events modulate protein activity. The results further provide the potential to predict likely cognate STPKs for newly identified phosphoproteins.

Full Text

Duke Authors

Cited Authors

  • Prisic, S; Dankwa, S; Schwartz, D; Chou, MF; Locasale, JW; Kang, C-M; Bemis, G; Church, GM; Steen, H; Husson, RN

Published Date

  • April 20, 2010

Published In

Volume / Issue

  • 107 / 16

Start / End Page

  • 7521 - 7526

PubMed ID

  • 20368441

Pubmed Central ID

  • 20368441

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.0913482107

Language

  • eng

Conference Location

  • United States