Specific activation of cdc25 tyrosine phosphatases by B-type cyclins: evidence for multiple roles of mitotic cyclins.
Two previously unidentified human cdc25 genes have been isolated, cdc25A and cdc25B. Both genes rescue a cdc25ts mutant of fission yeast. Microinjection of anti-cdc25A antibodies into HeLa cells causes their arrest in mitosis. cdc25A and cdc25B display endogenous tyrosine phosphatase activity that is stimulated several-fold, in the absence of cdc2, by stoichiometric addition of either cyclin B1 or B2 but not A or D1. Association between cdc25A and cyclin B1/cdc2 was detected in the HeLa cells. These findings indicate that B-type cyclins are multifunctional proteins that not only act as M phase regulatory subunits of the cdc2 protein kinase, but also activate the cdc25 tyrosine phosphatase, of which cdc2 is the physiological substrate. A region of amino acid similarity between cyclins and tyrosine PTPases has been detected. This region is absent in cdc25 phosphatases. The motif may represent an activating domain that has to be provided to cdc25 by intermolecular interaction with cyclin B.
Galaktionov
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Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724.
Beach
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D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D016213:Cyclins / Q000494:pharmacology*; D004247:DNA / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D005816:Genetic Complementation Test; D006367:HeLa Cells; D006801:Humans; D007158:Immunologic Techniques; D066298:In Vitro Techniques; D008938:Mitosis; D008969:Molecular Sequence Data; D005810:Multigene Family; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism* / Q000502:physiology*; D011506:Proteins / Q000502:physiology*; D012568:Schizosaccharomyces / Q000235:genetics; D016415:Sequence Alignment; D020687:cdc25 Phosphatases
D016213:Cyclins; D011506:Proteins; D004247:DNA; D017027:Protein Tyrosine Phosphatases; D020687:cdc25 Phosphatases