Dephosphorylation of cdc2 on threonine 161 is required for cdc2 kinase inactivation and normal anaphase.

Lorca, Thierry; Labbé, Jean‐Claude; Devault, Alain; Fesquet, Didier; Capony, Jean‐Paul; Cavadore, Jean‐Claude; Bouffant, Françoise Le; Dorée, Marcel

doi:10.1002/j.1460-2075.1992.tb05302.x

Cited by 143 publications

(94 citation statements)

References 66 publications

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“…More recently, a dual specificity phosphatase KAP (also called Cdi1, Cip2) was identified by its interaction with Cdc2, Cdk2, and Cdk3 in a yeast two-hybrid system (Gyuris et al 1993;Harper et al 1993;Hannon et al 1994). KAP dephosphorylated Thr-160 in human Cdk2 in vitro and preferred monomeric rather than cyclin-bound Cdk2 as a substrate (Poon and Hunter 1995), which is consistent with the observation that Xenopus Cdc2 is dephosphorylated only after cyclin degradation (Lorca et al 1992). However, no obvious KAP homolog exists in the budding yeast genome.…”

supporting

confidence: 77%

“…For example, studies from S. pombe and Xenopus show that the activating phosphorylation of Cdc2 is removed rapidly either during or at the end of mitosis (Gould et al 1991;Lorca et al 1992). In S. cerevisiae, however, Cdc28p remains largely phosphorylated at Thr-169 throughout the cell cycle (Morgan 1997;Espinoza et al 1998; K. Ross, P. Kaldis, and M.J. Solomon, unpubl.…”

Section: Cak Vs Pp2cmentioning

confidence: 99%

“…Studies in Schizosaccharomyces pombe and Xenopus egg extracts raised the possibility that the dephosphorylation of this residue may be required for exit from mitosis (Gould et al 1991;Lorca et al 1992), and implicated type 2A and type 1 protein phosphatases in the dephosphorylation of Cdc2 (Lee et al 1991;Lorca et al 1992). More recently, a dual specificity phosphatase KAP (also called Cdi1, Cip2) was identified by its interaction with Cdc2, Cdk2, and Cdk3 in a yeast two-hybrid system (Gyuris et al 1993;Harper et al 1993;Hannon et al 1994).…”

mentioning

confidence: 99%

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Dephosphorylation of cyclin-dependent kinases by type 2C protein phosphatases

Cheng¹,

Ross²,

Kaldis³

et al. 1999

Genes & Development

156

152

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Activating phosphorylation of cyclin-dependent protein kinases (CDKsEukaryotic cell cycle progression is controlled by the sequential activation and inactivation of cyclin-dependent protein kinases (CDKs). To coordinate the cell cycle machinery, extracellular and intracellular signals regulate CDK activities through a variety of mechanisms, including association with regulatory subunits (cyclins, inhibitors, and assembly factors), subcellular localization, transcriptional regulation, selective proteolysis, and reversible protein phosphorylation

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supporting

confidence: 77%

Section: Cak Vs Pp2cmentioning

confidence: 99%

mentioning

confidence: 99%

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Dephosphorylation of cyclin-dependent kinases by type 2C protein phosphatases

Cheng¹,

Ross²,

Kaldis³

et al. 1999

Genes & Development

156

152

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“…Cyclin A was overexpressed in E. coli and purified to homogeneity as described by Lorca et al (42). Fluorescence measurements were performed at 25°C using a Spex II fluorolog spectrofluorometer, with spectral band passes of 2 and 8 nm, for excitation and emission, respectively.…”

Section: Analysis Of Cdk/nucleotide Interactionsmentioning

confidence: 99%

Effects of Phosphorylation of Threonine 160 on Cyclin-dependent Kinase 2 Structure and Activity

Brown

Noble

Lawrie

et al. 1999

Journal of Biological Chemistry

222

197

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We have prepared phosphorylated cyclin-dependent protein kinase 2 (CDK2) for crystallization using the CDK-activating kinase 1 (CAK1) from Saccharomyces cerevisiae and have grown crystals using microseeding techniques. Phosphorylation of monomeric human CDK2 by CAK1 is more efficient than phosphorylation of the binary CDK2-cyclin A complex. Phosphorylated CDK2 exhibits histone H1 kinase activity corresponding to approximately 0.3% of that observed with the fully activated phosphorylated CDK2-cyclin A complex. Fluorescence measurements have shown that Thr 160 phosphorylation increases the affinity of CDK2 for both histone substrate and ATP and decreases its affinity for ADP. By contrast, phosphorylation of CDK2 has a negligible effect on the affinity for cyclin A. The crystal structures of the ATP-bound forms of phosphorylated CDK2 and unphosphorylated CDK2 have been solved at 2.1-Å resolution. The structures are similar, with the major difference occurring in the activation segment, which is disordered in phosphorylated CDK2. The greater mobility of the activation segment in phosphorylated CDK2 and the absence of spontaneous crystallization suggest that phosphorylated CDK2 may adopt several different mobile states. The majority of these states are likely to correspond to inactive conformations, but a small fraction of phosphorylated CDK2 may be in an active conformation and hence explain the basal activity observed.

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“…That the inactivation of mitotic kinase is necessary for exit is suggested by the observation that expression of nondestructible cyclin B causes lateanaphase arrest in S. cerevisiae (58). Studies of Xenopus egg extracts concluded that both cyclin destruction and dephosphorylation of Thr-161 are required to inactivate the cdc2-cyclin B complex (29). In S. pombe, cells overexpressing the cdc2 allele in which Thr-167 has been replaced by glutamic acid accumulate multiple nuclei, become multiseptated, and eventually arrest with short mitotic spindles (24).…”

mentioning

confidence: 99%

Dephosphorylation of Threonine 169 of Cdc28 Is Not Required for Exit from Mitosis but May Be Necessary for Start in Saccharomyces cerevisiae

Lim

Loy

Zaman

et al. 1996

Molecular and Cellular Biology

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Entry into mitosis requires activation of cdc2 kinase brought on by its association with cyclin B, phosphorylation of the conserved threonine (Thr-167 in Schizosaccharomyces pombe) in the T loop, and dephosphorylation of the tyrosine residue at position 15. Exit from mitosis, on the other hand, is induced by inactivation of cdc2 activity via cyclin destruction. It has been suggested that in addition to cyclin degradation, dephosphorylation of Thr-167 may also be required for exit from the M phase. Here we show that Saccharomyces cerevisiae cells expressing cdc28-E169 (a CDC28 allele in which the equivalent threonine, Thr-169, has been replaced by glutamic acid) are able to degrade mitotic cyclin Clb2, inactivate the Cdc28/Clb2 kinase, and disassemble the anaphase spindles, suggesting that they exit mitosis normally. The cdc28-E169 allele is active with respect to its mitotic functions, since it complements the mitosis-defective cdc28-1N allele. Whereas replacement of Thr-169 with serine affects neither Start nor the mitotic activity of Cdc28, replacement with glutamic acid or alanine renders Cdc28 inactive for Start-related functions. Coimmunoprecipitation experiments show that although Cdc28-E169 associates with mitotic cyclin Clb2, it fails to associate with the G 1 cyclin Cln2. Thus, an unmodified threonine at position 169 in Cdc28 is important for interaction with G 1 cyclins. We propose that in S. cerevisiae, dephosphorylation of Thr-169 is not required for exit from mitosis but may be necessary for commitment to the subsequent division cycle.

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Dephosphorylation of cdc2 on threonine 161 is required for cdc2 kinase inactivation and normal anaphase.

Cited by 143 publications

References 66 publications

Dephosphorylation of cyclin-dependent kinases by type 2C protein phosphatases

Dephosphorylation of cyclin-dependent kinases by type 2C protein phosphatases

Effects of Phosphorylation of Threonine 160 on Cyclin-dependent Kinase 2 Structure and Activity

Dephosphorylation of Threonine 169 of Cdc28 Is Not Required for Exit from Mitosis but May Be Necessary for Start in Saccharomyces cerevisiae

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