Regulation of the cdc25 protein during the cell cycle in Xenopus extracts.
The cdc25 protein is a highly specific tyrosine phosphatase that triggers mitosis by dephosphorylating the cdc2 protein kinase. Using Xenopus extracts, we have found that the cdc25 protein is active at a low level throughout interphase. Near the onset of mitosis, the cdc25 protein undergoes a marked elevation in phosphatase activity that coincides with an extensive phosphorylation of the protein in its N-terminal region. In vitro dephosphorylation of this hyperphosphorylated form of cdc25 reduces its phosphatase activity back to the interphase level. Moreover, treatment of interphase Xenopus extracts with okadaic acid, a phosphatase inhibitor that accelerates the entry into mitosis, elicits both the premature hyperphosphorylation of cdc25 and the stimulation of its cdc2-specific tyrosine phosphatase activity. These experiments demonstrate the existence of a cdc25 regulatory system consisting of both a stimulatory kinase that phosphorylates a putative regulatory domain of the cdc25 protein and an inhibitory serine/threonine phosphatase that counteracts this kinase activity.
Kumagai
A
A
Division of Biology, California Institute of Technology, Pasadena 91125.
Dunphy
W G
WG
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004789:Enzyme Activation / Q000187:drug effects; D004794:Enzyme Repression / Q000187:drug effects; D004988:Ethers, Cyclic / Q000494:pharmacology; D008938:Mitosis; D008969:Molecular Sequence Data; D019319:Okadaic Acid; D016366:Open Reading Frames; D010063:Ovum / Q000201:enzymology; D010766:Phosphorylation; D014176:Protein Biosynthesis; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011506:Proteins / Q000037:antagonists & inhibitors; D014981:Xenopus / Q000502:physiology; D020687:cdc25 Phosphatases
D004988:Ethers, Cyclic; D011506:Proteins; D019319:Okadaic Acid; D017027:Protein Tyrosine Phosphatases; D020687:cdc25 Phosphatases