AfsR as an integrator of signals that are sensed by multiple serine/threonine kinases in Streptomyces coelicolor A3(2).
The genome sequence of Streptomyces coelicolor A3(2) has revealed the presence of about 40 protein serine/threonine or tyrosine kinases. AfsK, which is able to phosphorylate AfsR, a transcriptional activator with ATPase activity, represents the first instance in which a bacterial Hanks-type protein kinase phosphorylates a specific protein and exerts biologically important functions. The AfsK-AfsR system in S. coelicolor A3(2) globally controls secondary metabolism. The signal transduction pathway so far demonstrated or suggested is as follows: AfsK loosely attached to the membrane autophosphorylates threonine and serine residues, perhaps on sensing some external stimulus, and enhances its kinase activity. The kinase activity is modulated by KbpA, an AfsK-binding protein, by means of protein-protein interactions. The activated AfsK phosphorylates threonine and serine residues of AfsR in the cytoplasm, by which the DNA-binding activity of AfsR is greatly enhanced. In addition to AfsK, other kinases-including PkaG and AfsL-also phosphorylate AfsR, suggesting that AfsR serves as an integrator of multiple signals sensed by these kinases. The phosphorylated AfsR binds the promoter of afsS, which encodes a protein of 63 amino acids, and forms a closed complex with RNA polymerase. The closed complex is then converted to a transcriptionally active open complex by the energy available from ATP hydrolysis by AfsR. AfsS induced in this way activates transcription of pathway-specific transcriptional activators, such as actII-ORF4 for actinorhodin production and redD for undecylprodigiosin, in an as yet unknown manner.
Horinouchi
Sueharu
S
Department of Biotechnology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Bunkyo-ku, 113-8657 Tokyo, Japan. asuhori@mail.ecc.u-tokyo.ac.jp
D001426:Bacterial Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013302:Streptomyces / Q000201:enzymology*; D014157:Transcription Factors / Q000378:metabolism*
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C066581:AfsR protein, Streptomyces coelicolor; D017346:Protein Serine-Threonine Kinases