Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Mutants at Ser277 of Xenopus cdc2 protein kinase induce oocyte maturation in the absence of the positive regulatory phosphorylation site Thr161.
Pickham KM
,
Donoghue DJ
.
???displayArticle.abstract???
The cdc2 protein kinase is an important regulatory protein for both meiosis and mitosis. Previously, we demonstrated that simultaneous mutation of Thr14-->Ala14 and Tyr15-->Phe15 in the Xenopus cdc2 protein results in an activated cdc2 mutant that induces maturation in resting oocytes. In addition, we confirmed the importance of the positive regulatory phosphorylation site, Thr161, by demonstrating that cdc2 mutants containing additional mutations of Thr161-->Ala161 or Glu161 are inactive in the induction of oocyte maturation. Here, we have analyzed the importance of an additional putative cdc2 phosphorylation site,Ser277. Single mutation of Ser277-->Asp277 or Ala277 had no effect on activity, and these mutants were unable to induce Xenopus oocyte maturation. However, the double mutant Ala161/Asp277 was capable of inducing oocyte maturation, suggesting that mutation of Ser277-->Asp277 could compensate for the mutation of Thr161-->Ala161. The Asp277 mutation could also compensate for the Ala161 mutation in the background of the activating mutations Ala14/Phe15. Although mutants containing the compensatory Ala161 and Asp277 mutations were capable of inducing oocyte maturation, these mutant cdc2 proteins lacked detectable in vitro kinase activity. Tryptic phosphopeptide mapping of mutant cdc2 protein and comparison with in vitro synthesized peptides indicated that Ser277 is not a major site of phosphorylation in Xenopus oocytes; however, we cannot rule out the possibility of phosphorylation at this site in a biologically active subpopulation of cdc2 molecules. The data presented here, together with prior reports of Ser277 phosphorylation in somatic cells, suggest an important role for Ser277 in the regulation of cdc2 activity. The regulatory role of Ser277 most likely involves its indirect effects on the nearby residue Arg275, which participates in a structurally important ion pair with Glu173, which lies in the same loop as Thr161 in the cdc2 protein.
Boyle,
Phosphopeptide mapping and phosphoamino acid analysis by two-dimensional separation on thin-layer cellulose plates.
1991, Pubmed
Boyle,
Phosphopeptide mapping and phosphoamino acid analysis by two-dimensional separation on thin-layer cellulose plates.
1991,
Pubmed
De Bondt,
Crystal structure of cyclin-dependent kinase 2.
1993,
Pubmed
Ducommun,
cdc2 phosphorylation is required for its interaction with cyclin.
1991,
Pubmed
,
Xenbase
Dunphy,
The Xenopus cdc2 protein is a component of MPF, a cytoplasmic regulator of mitosis.
1988,
Pubmed
,
Xenbase
Featherstone,
Fission yeast p107wee1 mitotic inhibitor is a tyrosine/serine kinase.
1991,
Pubmed
Fesquet,
The MO15 gene encodes the catalytic subunit of a protein kinase that activates cdc2 and other cyclin-dependent kinases (CDKs) through phosphorylation of Thr161 and its homologues.
1993,
Pubmed
,
Xenbase
Freeman,
Meiotic induction by Xenopus cyclin B is accelerated by coexpression with mosXe.
1991,
Pubmed
,
Xenbase
Gabrielli,
Cdc25 regulates the phosphorylation and activity of the Xenopus cdk2 protein kinase complex.
1992,
Pubmed
,
Xenbase
Gautier,
cdc25 is a specific tyrosine phosphatase that directly activates p34cdc2.
1991,
Pubmed
,
Xenbase
Gautier,
Purified maturation-promoting factor contains the product of a Xenopus homolog of the fission yeast cell cycle control gene cdc2+.
1988,
Pubmed
,
Xenbase
Gould,
Phosphorylation at Thr167 is required for Schizosaccharomyces pombe p34cdc2 function.
1991,
Pubmed
Hanks,
The protein kinase family: conserved features and deduced phylogeny of the catalytic domains.
1988,
Pubmed
Kinoshita,
Distinct, essential roles of type 1 and 2A protein phosphatases in the control of the fission yeast cell division cycle.
1990,
Pubmed
Knighton,
Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase.
1991,
Pubmed
Kobayashi,
On the synthesis and destruction of A- and B-type cyclins during oogenesis and meiotic maturation in Xenopus laevis.
1991,
Pubmed
,
Xenbase
Krek,
Mutations of p34cdc2 phosphorylation sites induce premature mitotic events in HeLa cells: evidence for a double block to p34cdc2 kinase activation in vertebrates.
1991,
Pubmed
Krek,
Differential phosphorylation of vertebrate p34cdc2 kinase at the G1/S and G2/M transitions of the cell cycle: identification of major phosphorylation sites.
1991,
Pubmed
Kunkel,
Rapid and efficient site-specific mutagenesis without phenotypic selection.
1985,
Pubmed
Lee,
INH, a negative regulator of MPF, is a form of protein phosphatase 2A.
1991,
Pubmed
,
Xenbase
Lee,
cdc25+ encodes a protein phosphatase that dephosphorylates p34cdc2.
1992,
Pubmed
,
Xenbase
Lew,
Isolation of three novel human cyclins by rescue of G1 cyclin (Cln) function in yeast.
1991,
Pubmed
Lorca,
Dephosphorylation of cdc2 on threonine 161 is required for cdc2 kinase inactivation and normal anaphase.
1992,
Pubmed
,
Xenbase
Luo,
Transfer of proteins to membranes facilitates both cyanogen bromide cleavage and two-dimensional proteolytic mapping.
1990,
Pubmed
Maller,
Xenopus oocytes and the biochemistry of cell division.
1990,
Pubmed
,
Xenbase
Marcote,
A three-dimensional model of the Cdc2 protein kinase: localization of cyclin- and Suc1-binding regions and phosphorylation sites.
1993,
Pubmed
Masui,
Cytoplasmic control of nuclear behavior during meiotic maturation of frog oocytes.
1971,
Pubmed
Matsushime,
Identification and properties of an atypical catalytic subunit (p34PSK-J3/cdk4) for mammalian D type G1 cyclins.
1992,
Pubmed
Meyerson,
A family of human cdc2-related protein kinases.
1992,
Pubmed
Norbury,
Regulatory phosphorylation of the p34cdc2 protein kinase in vertebrates.
1991,
Pubmed
,
Xenbase
Nurse,
Universal control mechanism regulating onset of M-phase.
1990,
Pubmed
Parker,
p107wee1 is a dual-specificity kinase that phosphorylates p34cdc2 on tyrosine 15.
1992,
Pubmed
Parker,
Cyclin promotes the tyrosine phosphorylation of p34cdc2 in a wee1+ dependent manner.
1991,
Pubmed
Pickham,
Requirement of mosXe protein kinase for meiotic maturation of Xenopus oocytes induced by a cdc2 mutant lacking regulatory phosphorylation sites.
1992,
Pubmed
,
Xenbase
Pines,
p34cdc2: the S and M kinase?
1990,
Pubmed
Pines,
Molecular cloning and characterization of the mRNA for cyclin from sea urchin eggs.
1987,
Pubmed
,
Xenbase
Poon,
The cdc2-related protein p40MO15 is the catalytic subunit of a protein kinase that can activate p33cdk2 and p34cdc2.
1993,
Pubmed
,
Xenbase
Solomon,
CAK, the p34cdc2 activating kinase, contains a protein identical or closely related to p40MO15.
1993,
Pubmed
,
Xenbase
Solomon,
Role of phosphorylation in p34cdc2 activation: identification of an activating kinase.
1992,
Pubmed
,
Xenbase
Swenson,
The clam embryo protein cyclin A induces entry into M phase and the resumption of meiosis in Xenopus oocytes.
1986,
Pubmed
,
Xenbase
Tachibana,
The starfish egg mRNA responsible for meiosis reinitiation encodes cyclin.
1990,
Pubmed
,
Xenbase
Westendorf,
The role of cyclin B in meiosis I.
1989,
Pubmed
,
Xenbase