A novel bacterial tyrosine kinase essential for cell division and differentiation

Protein kinases play central roles in the regulation of eukaryotic and prok aryotic cell growth, division, and differentiation. The Caulobacter crescen tus divL gene encodes a novel bacterial tyrosine kinase essential for cell viability and division. Although the DivL protein is homologous to the ubiq uitous bacterial histidine protein kinases (HPKs), it differs from previous ly studied members of this protein kinase family in that it contains a tyro sine residue (Tyr-550) in the conserved H-box instead of a histidine residu e, which is the expected site of autophosphorylation. DivL is autophosphory lated on Tyr-550 in vitro, and this tyrosine residue is essential for cell viability and regulation of the cell division cycle. Purified DivL also cat alyzes phosphorylation of CtrA and activates transcription in vitro of the cell cycle-regulated fliF promoter. Suppressor mutations in ctrA bypass the conditional cell division phenotype of cold-sensitive divL mutants, provid ing genetic evidence that DivL function in cell cycle and developmental reg ulation is mediated, at least in part, by the global response regulator Ctr A. DivL is the only reported HPK homologue whose function has been shown to require autophosphorylation on a tyrosine, and, thus, it represents a new class of kinases within this superfamily of protein kinases.