Journal
GENES & DEVELOPMENT
Volume 19, Issue 14, Pages 1692-1704Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1311105
Keywords
kinase; DivIVA; peptide library screen; mycobacteria
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Funding
- NIAID NIH HHS [R21 AI051707, AI51707, K08-AI53819, R01 AI059702, AI59702, K08 AI053819, R01 AI037901] Funding Source: Medline
- NIGMS NIH HHS [GM56203, R01 GM056203] Funding Source: Medline
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The Mycobacterium tuberculosis genome contains 11 serine/threonine kinase genes including two, pknA and pknB, that are part of an operon encoding genes involved in cell shape control and cell wall synthesis. Here we demonstrate that pknA and pknB are predominantly expressed during exponential growth, and that overexpression of these kinases slows growth and alters cell morphology. We determined the preferred substrate motifs of PknA and PknB, and identified three in vivo substrates of these kinases: PknB; Wag31, an ortholog of the cell division protein DivIVA; and Rv1422, a conserved protein of unknown function. Expression of different alleles of wag31 in vivo alters cell shape, in a manner dependent on the phosphoacceptor residue in the protein produced. Partial depletion of pknA or pknB results in narrow, elongated cells. These data indicate that signal transduction mediated by these kinases is a novel mechanism for the regulation of cell shape in mycobacteria, one that may be conserved among gram-positive bacteria.
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