Effects of protein kinase inhibitors on in vitro protein phosphorylation and cellular differentiation of Streptomyces griseus.
In vitro phosphorylation reactions using extracts of Streptomyces griseus cells and gamma-[32P]ATP revealed the presence of multiple phosphorylated proteins. Most of the phosphorylations were distinctly inhibited by staurosporine and K-252a which are known to be eukaryotic protein kinase inhibitors. The in vitro experiments also showed that phosphorylation was greatly enhanced by manganese and inhibition of phosphorylation by staurosporine and K-252a was partially circumvented by 10 mM manganese. A calcium-activated protein kinase(s) was little affected by these inhibitors. Herbimycin and radicicol, known to be tyrosine kinase inhibitors, completely inhibited the phosphorylation of one protein. Consistent with their in vitro effects the protein kinase inhibitors inhibited aerial mycelium formation and pigment production by S. griseus. All these data suggest that S. griseus possesses several protein kinases of eukaryotic type which are essential for morphogenesis and secondary metabolism. In vitro phosphorylation of some proteins in a staurosporine-producing Streptomyces sp. was also inhibited by staurosporine, K-252a and herbimycin, which suggests the presence of a mechanism for self-protection in this microorganism.
Hong
S K
SK
Department of Agricultural Chemistry, Faculty of Agriculture, University of Tokyo, Japan.
Matsumoto
A
A
Horinouchi
S
S
Beppu
T
T
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D016227:Benzoquinones; D002227:Carbazoles / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D005656:Fungal Proteins / Q000378:metabolism*; D026121:Indole Alkaloids; D007546:Isoquinolines / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D008345:Manganese / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D019311:Staurosporine; D013305:Streptomyces griseus / Q000502:physiology*
D000470:Alkaloids; D016227:Benzoquinones; D002227:Carbazoles; D005656:Fungal Proteins; D026121:Indole Alkaloids; D007546:Isoquinolines; D047029:Lactams, Macrocyclic; D010446:Peptide Fragments; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011809:Quinones; D017828:Rifabutin; D008345:Manganese; C020754:herbimycin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C049985:staurosporine aglycone; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D019311:Staurosporine