Cancer Osaka thyroid (Cot) phosphorylates Polo-like kinase (PLK1) at Ser137 but not at Thr210.
Cancer Osaka thyroid (Cot) is a proto-oncogenic kinase which belongs to the MAP3K family. A peptide-based substrate screening assay revealed that Cot has the ability to phosphorylate Polo-like kinase 1 (Plk1) at Ser137. Kinase assays with intact Plk1 and peptides surrounding Ser137 and Thr210 indicated further that Cot phosphorylates Ser137 but not Thr210. Additional support came from 3D peptide structure prediction and Cot-Plk1 interaction modeling. In vivo experiments demonstrated that wild type Cot, but not a kinase-dead mutant, has the ability to phosphorylate Ser137. Knockdown of Cot in Hela showed a reduction in the level of phosphorylation of Ser137. These results imply for the first time that Cot might be an upstream kinase of Plk1 and suggest a new mechanism for the regulation of the cellular function of Plk1.
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
Binhui
B
Wu
Ping
P
Jiang
Yuguang
Y
Mu
Rupert C
RC
Wilmouth
D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D012694:Serine / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D013912:Threonine / Q000235:genetics / Q000378:metabolism; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D020930:MAP Kinase Kinase Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D012694:Serine; D013912:Threonine; D000097869:Polo-Like Kinase 1; C069937:MAP3K8 protein, human