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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The p34cdc2 protein kinase is a key component in the regulation of the eukaryotic cell cycle and has been conserved during evolution. We have isolated cDNA clones corresponding to a cdc2 gene (cdc2Pa) from the conifer Norway spruce, Picea abies (L.) Karst. The deduced amino acid sequence is 85-90% identical to p34cdc2 homologues from other plants, contains eleven subdomains characteristic for the protein kinase family, and three sequence motifs specific for the cdc2 protein kinases. A partial genomic clone of cdc2Pa reveals two introns at positions identical to intron positions in Arabidopsis thaliana cdc2a. A Southern blot analysis shows that cdc2Pa is a single-copy gene belonging to a family of about 10 related genes. Partial genomic sequences of six of the genes in this family (86-92% identical to cdc2Pa) show distinct features of processed retropseudogenes. These lack introns and contain deletions, insertions and/or non-silent point mutations. This result is consistent with the hypothesis that processed retropseudogenes in plants may be common among genes expressed in the apical meristem, that is, in cells which have the potential to take part in the formation of reproductive organs. Although cdc2Pa transcripts were abundant in the epicotyl and thus likely in the apical meristem, we observed no strict coupling of expression to cell division in embryos and seedlings.
Plant Mol Biol 1995 Jan
PMID:A cdc2 homologue and closely related processed retropseudogenes from Norway spruce. 788 27

suc1 is an essential gene initially identified for its ability to rescue certain temperature-sensitive alleles of cdc2 in Schizosaccharomyces pombe. The role of suc1 in the regulation of the cdc2 kinase is not well understood. In our study, we have characterized the biochemical effect of loss of suc1 function on specific cdc2-cyclin complexes. We show that the cig1 cyclin is associated with cdc2 and that the cdc2-cig1 kinase is activated at mitosis, with kinetics similar to those of the cdc2-cdc13 kinase. We provide evidence that loss of suc1 function affects the kinase activity of the two distinct mitotic forms of the cdc2 kinase. We also show that a dramatic increase in the level of the cdc13 protein is associated with loss of suc1. These results suggest that mitosis cannot be properly completed in the absence of suc1, possibly because of an increase in the level of cdc2-cdc13 complex, and support the idea of a role for suc1 in the regulation of multiple forms of the cdc2 kinase.
Mol Cell Biol 1995 Apr
PMID:p13suc1 of Schizosaccharomyces pombe regulates two distinct forms of the mitotic cdc2 kinase. 789 98

We have recently shown that two proteins, proliferating cell nuclear antigen (PCNA) and p21, are associated with cyclin D. Here we show that PCNA and p21 are common components of a wide variety of cyclin/cyclin-dependent kinase complexes in nontransformed cells. These include kinase complexes containing cyclin A, cyclin B, and cyclin D, associated either with CDC2, CDK2, CDK4, or CDK5. We show that PCNA and p21 form separate quaternary complex with each cyclin/CDK and that these quaternary complexes contain a substantial, if not major, fraction of the cell cycle kinases in asynchronously growing cells. These results suggest that PCNA and p21 may perform a common function for all these kinases.
Mol Biol Cell 1993 Sep
PMID:Proliferating cell nuclear antigen and p21 are components of multiple cell cycle kinase complexes. 790 56

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.
Mol Biol Cell 1994 May
PMID:Mutants at Ser277 of Xenopus cdc2 protein kinase induce oocyte maturation in the absence of the positive regulatory phosphorylation site Thr161. 791 39

Differentiation of murine erythroleukemia cells induced by hexamethylene bisacetamide (HMBA) is associated with accumulation of underphosphorylated retinoblastoma protein (pRB) and an increase in retinoblastoma (RB) gene expression. Here we show that HMBA causes a rapid decrease in the level of cyclin-dependent kinase 4 (cdk4) protein. This decrease results from decreased stability of the protein, while the rate of synthesis of the protein is not affected by HMBA. The decrease in the level of cdk4 protein is followed by suppression of the pRB kinase activity associated with cdk4. Cyclin D3, which can bind and activated cdk4, is increased in HMBA-induced cells and is found in complex with pRB and the transcription factor E2F. In uninduced cells cyclin D3 complexes with pRB and E2F are barely detected. At the later stages of differentiation, MEL cells become arrested in G1 and cdk2 kinase activity is suppressed; this is accompanied by a decrease in the level of cyclin A and cdk2 proteins. Cells transfected with cdk4, which continue to overexpress cdk4 protein during culture with HMBA, are resistant to HMBA-induced differentiation. In contrast, overexpression of cdk2 protein does not inhibit induced differentiation. These findings suggest that suppression of cdk4 is a critical event in the pathway leading to terminal differentiation of erythroleukemia cells.
Mol Cell Biol 1994 Nov
PMID:Suppression of cyclin-dependent kinase 4 during induced differentiation of erythroleukemia cells. 793 34

Herpesvirus saimiri contains an open reading frame called eclf2 with homology to the cellular type D cyclins. We now show that the eclf2 gene product is a novel virus-encoded cyclin (v-cyclin). The protein encoded by the v-cyclin gene of this oncogenic herpesvirus was found to have an apparent molecular size of 29 kDa in transformed cells. v-Cyclin protein was found to be associated with cdk6, a cellular cyclin-dependent kinase known to interact with cellular type D cyclins. cdk6/v-cyclin complexes strongly phosphorylated Rb fusion protein and histone H1 as substrates in vitro. Mutational analyses showed that highly conserved amino acids in the cyclin box of v-cyclin were important for association with cdk6 and for activation of cdk6 kinase activity. Thus, v-cyclin resembles cellular type D cyclins in primary sequence, in its association with cdk6, by its ability to activate protein kinase activity, and by the presence of functional cyclin box sequences. v-Cyclin exhibited a selective preference for association with cdk6 over other cyclin-dependent kinases and a high level of kinase activation. The properties of v-cyclin suggest a likely role in oncogenic transformation by this T-lymphotropic herpesvirus.
Mol Cell Biol 1994 Nov
PMID:Virus-encoded cyclin. 793 38

The assembly of functional holoenzymes composed of regulatory D-type cyclins and cyclin-dependent kinases (cdks) is rate limiting for progression through the G1 phase of the mammalian somatic cell cycle. Complexes between D-type cyclins and their major catalytic subunit, cdk4, are catalytically inactive until cyclin-bound cdk4 undergoes phosphorylation on a single threonyl residue (Thr-172). This step is catalyzed by a cdk-activating kinase (CAK) functionally analogous to the enzyme which phosphorylates cdc2 and cdk2 at Thr-161/160. Here, we demonstrate that the catalytic subunit of mouse cdc2/cdk2 CAK (a 39-kDa protein designated p39MO15) can assemble with a regulatory protein present in either insect or mammalian cells to generate a CAK activity capable of phosphorylating and enzymatically activating both cdk2 and cdk4 in complexes with their respective cyclin partners. A newly identified 37-kDa cyclin-like protein (cyclin H [R. P. Fisher and D. O. Morgan, Cell 78:713-724, 1994]) can assemble with p39MO15 to activate both cyclin A-cdk2 and cyclin D-cdk4 in vitro, implying that CAK is structurally reminiscent of cyclin-cdk complexes themselves. Antisera produced to the p39MO15 subunit can completely deplete mammalian cell lysates of CAK activity for both cyclin A-cdk2 and cyclin D-cdk4, with recovery of activity in the resulting immune complexes. By using an immune complex CAK assay, CAK activity for cyclin A-cdk2 and cyclin D-cdk4 was detected both in quiescent cells and invariantly throughout the cell cycle. Therefore, although it is essential for the enzymatic activation of cyclin-cdk complexes, CAK appears to be neither rate limiting for the emergence of cells from quiescence nor subject to upstream regulatory control by stimulatory mitogens.
Mol Cell Biol 1994 Nov
PMID:Activation of cyclin-dependent kinase 4 (cdk4) by mouse MO15-associated kinase. 793 41

The transcription factor E2F has been implicated in cell cycle control by virtue of its association with cyclins, cyclin-dependent kinases, and pRb-related tumor suppressor gene products. Eggs and embryos from the frog Xenopus laevis have been used to investigate the characteristics of E2F-like molecules in the Xenopus cell cycle and throughout early development. We find multiple E2F species in Xenopus eggs, at least one of which is modified by phosphorylation. The vast majority of E2F remains in the free form throughout the very early embryonic cell cycle, and it also remains predominantly free until some time after the mid-blastula transition, the onset of zygotic transcription. At this time, E2F complexes significantly to pRb but not to cdk2, although cdk2 binding is found in tissue culture cells from a very advanced stage in embryogenesis. This suggests that the complexing of E2F to cyclins, cyclin-dependent kinases, and tumor suppressor gene products may be controlled separately in early Xenopus development. Thus, the association of E2F with other molecules may not result solely from processes affecting cell cycle progression but may also reflect developmental and differentiation cues.
Mol Cell Biol 1994 Jul
PMID:E2F and its developmental regulation in Xenopus laevis. 800 93

Treatment of PHA-activated PBMC with anti-HLA class I monoclonal antibody (mAb 01.65) shows: 1) depletion of particulate protein Kinase C (PKC) and partial reduction of cytosolic PKC after only 10 min.; 2) inhibition of tritiated thymidine (3H-Td) incorporation; 3) slowing down of cell cycle; 4) reduced expression of four cell cycle related genes. These findings suggest that the depletion of PKC is reflected on the cell cycle progression and expression of cell cycle related genes. We studied, in PHA-activated PBMC cultures, the effect of N-N-Staurosporine (StSp) acting as PKC inhibitor at nanomolar concentrations, alone and combined with mAb 01.65. StSp, inhibits the proliferative response of PHA stimulated PBMC in a competitive fashion with mAb 01.65. We report here that StSp alone and combined with mAb 01.65 affects also the expression of c-myc and cdc2 and the membrane expression of two proliferation markers: IL-2R (CD25) and TfR (CD71).
Biochem Mol Biol Int 1994 Jan
PMID:Inhibition of protein kinase C in PHA-activated PBMC treated with anti-HLA class I monoclonal antibody is associated to decreased proliferation and expression of cell cycle related genes. 801 75

MPM-2 antigens, a discrete set of phosphoproteins that contain similar phosphoepitopes recognized by the monoclonal antibody MPM-2, are phosphorylated during M-phase induction. Our previous studies suggested that certain MPM-2 antigens are involved in the appearance of maturation-promoting factor (MPF) activity. Because the central mitotic regulator cdc2 kinase has been shown to exhibit MPF activity, we explored the possibility that certain MPM-2 antigens are regulators of cdc2 kinase. We found that MPM-2 binding of its antigens would inhibit the autoamplification of cdc2 kinase in Xenopus oocytes and interfere with cyclin-activation of cdc2 kinase in Xenopus interphase egg extract. Immunodepletion of MPM-2 antigens from cyclin-induced M-phase egg extract caused the inactivation of cdc2 kinase, which was accompanied by an inhibitory phosphorylation of p34cdc2 on Thr 14 and Tyr 15, indicating that at least one MPM-2 antigen is a positive regulator of p34cdc2 dephosphorylation. We then showed that cdc25 from M-phase arrested egg extract is an MPM-2 antigen. These results suggest that phosphorylation of the epitope recognized by MPM-2 may be a crucial event in the activation of cdc25 and that the kinase(s) that phosphorylates this MPM-2 epitope may be an important regulator of cdc2 kinase activation.
Mol Biol Cell 1994 Feb
PMID:cdc25 is one of the MPM-2 antigens involved in the activation of maturation-promoting factor. 801


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