A novel histidine kinase inhibitor regulating development in Bacillus subtilis.
Kinase A is the sensor histidine kinase responsible for processing postexponential phase information and providing phosphate input to the phosphorelay that activates developmental transcription via phosphorylated Spo0A. A protein inhibitor, KipI, of kinase A was discovered encoded in an operon of genes of unknown function but regulated by the availability of fixed nitrogen. KipI is a potent inhibitor of the autophosphorylation reaction of kinase A but does not inhibit phosphate transfer to the Spo0F response regulator once kinase A is phosphorylated. KipI is an inhibitor of the catalytic domain of kinase A affecting the ATP/ADP reactions and not the phosphotransferase functions of this domain. The inhibitory activity of KipI is counteracted by the product of another gene in the operon, KipA. This protein may bind to KipI, preventing its function as an inhibitor of kinase A. KipI may be the first representative of a new class of signal transduction inhibitors that function by direct interaction with the catalytic domain of histidine kinases to counteract signals influencing the "sensor" domain of such kinases. This inhibitor represents yet another way by which the phosphorelay signal transduction system is affected by negative regulators under the control of metabolic, environmental, or cell cycle influences antithetical to the initiation of developmental transcription.
Wang
L
L
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
Grau
R
R
Perego
M
M
Hoch
J A
JA
D001412:Bacillus subtilis / Q000201:enzymology* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005784:Gene Amplification; D015964:Gene Expression Regulation, Bacterial; D005947:Glucose / Q000494:pharmacology; D000071677:Histidine Kinase; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D009584:Nitrogen / Q000378:metabolism; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism; D010957:Plasmids; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D012097:Repressor Proteins; D015183:Restriction Mapping; D017384:Sequence Deletion; D015398:Signal Transduction / Q000502:physiology; D013171:Spores, Bacterial / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D015533:Transcriptional Activation / Q000502:physiology; D025521:Tumor Suppressor Proteins
D001426:Bacterial Proteins; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D047428:Protein Kinase Inhibitors; D012097:Repressor Proteins; C101458:ScgR protein, Bacillus subtilis; C080950:Spo0A protein, Bacillus subtilis; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D010770:Phosphotransferases; D011494:Protein Kinases; D000071677:Histidine Kinase; D005947:Glucose; D009584:Nitrogen