Activation of Xenopus Chk1 by mutagenesis of threonine-377.
Xenopus Chk1 (Xchk1) is required for the checkpoint-associated delay of the cell cycle in frog egg extracts containing unreplicated or UV-damaged DNA. Phosphorylation of Xchk1 at multiple sites in the SQ/TQ domain (residues 314-366) in response to unreplicated or UV-damaged DNA results in elevation of its kinase activity. We have found that mutagenesis of Thr-377 in the conserved Thr-Arg-Phe (TRF) motif of Xchk1 also leads to a substantial increase in kinase activity. Thr-377 does not appear to be a site of phosphorylation in Xchk1. These findings suggest that Thr-377 may play a role in suppressing the activity of Xchk1.
Wang
S X
SX
Division of Biology 216-76, Howard Hughes Medical Institute, California Institute of Technology, 1200 East California Blvd., Pasadena, CA 91125, USA.
Dunphy
W G
WG
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002453:Cell Cycle; D000071877:Checkpoint Kinase 1; D004330:Drosophila / Q000201:enzymology; D004789:Enzyme Activation; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000166:cytology; D011494:Protein Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012568:Schizosaccharomyces / Q000201:enzymology; D029702:Schizosaccharomyces pombe Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013912:Threonine; D014981:Xenopus; D029867:Xenopus Proteins
D011994:Recombinant Proteins; D029702:Schizosaccharomyces pombe Proteins; D029867:Xenopus Proteins; D013912:Threonine; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; C000605875:Chek1 protein, Xenopus; C000605873:Chk1 protein, S pombe