The Mycobacterium tuberculosis serine/threonine kinases PknA and PknB: substrate identification and regulation of cell shape.
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.
Division of Infectious Diseases, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA.
Choong-Min
CM
Kang
Derek W
DW
Abbott
Sang Tae
ST
Park
Christopher C
CC
Dascher
Lewis C
LC
Cantley
Robert N
RN
Husson
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D015964:Gene Expression Regulation, Bacterial; D018507:Gene Expression Regulation, Developmental; D005798:Genes, Bacterial; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000166:cytology* / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D019151:Peptide Library; D010641:Phenotype; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
D001426:Bacterial Proteins; D019151:Peptide Library; C451020:PknA protein, Mycobacterium tuberculosis; C475060:PknB protein, Mycobacterium tuberculosis; D017346:Protein Serine-Threonine Kinases