Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.22 (cdc2)
 8,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TC4, a ras-like G protein, has been implicated in the feedback pathway linking the onset of mitosis to the completion of DNA replication. In this report we find distinct roles for TC4 in both nuclear assembly and cell cycle progression. Mutant and wild-type forms of TC4 were added to Xenopus egg extracts capable of assembling nuclei around chromatin templates in vitro. We found that a mutant TC4 protein defective in GTP binding (GDP-bound form) suppressed nuclear growth and prevented DNA replication. Nuclear transport under these conditions approximated normal levels. In a separate set of experiments using a cell-free extract of Xenopus eggs that cycles between S and M phases, the GDP-bound form of TC4 had dramatic effects, blocking entry into mitosis even in the complete absence of nuclei. The effect of this mutant TC4 protein on cell cycle progression is mediated by phosphorylation of p34cdc2 on tyrosine and threonine residues, negatively regulating cdc2 kinase activity. Therefore, we provide direct biochemical evidence for a role of TC4 in both maintaining nuclear structure and in the signaling pathways that regulate entry into mitosis.
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PMID:Evidence for a dual role for TC4 protein in regulating nuclear structure and cell cycle progression. 818 41

Elongation factor-1 (EF-1) is a major substrate for cdc2 kinase in Xenopus oocytes. The guanine-nucleotide exchange factor EF-1 beta gamma delta, appears to have a highly complex macromolecular structure containing several GTP/GDP exchange proteins, valyl-tRNA synthetase, and a putative anchoring protein EF-1 gamma. During meiotic cell division, the factor becomes phosphorylated by cdc2 kinase, not only on EF-1 gamma, but also on two different phospho-acceptors on EF-1 delta. Phosphorylation is concomitant with changes in protein synthesis in vivo. Xenopus oocytes, and potentially all cells, contain a multitude of heteromeric forms of the complex which postulates that EF-1 beta gamma delta is not a "house keeping" factor but a sophisticated regulatory element.
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PMID:Phosphorylation of elongation factor-1 (EF-1) by cdc2 kinase. 955 69

The aim of these investigations was to identify a number of molecular markers that correlate to growth stimulation by IGF-I. For this purpose, we have selected four cell lines that respond equally well to growth stimulation by serum, but differ in their proliferative response to IGF-I. Two cell lines (R503 and R600 cells) respond to IGF-I with both DNA synthesis and cell division, a third cell line (R508 cells) can enter S phase after IGF-I, but the cells do not divide, and a fourth one (R12 cells) totally fails to respond to IGF-I with growth. Using these cell lines, all of which had an intact mitogenic response program to serum, we show that: (1) an increase in GTP/GDP ratio is an early event that distinguishes cells capable of entering S phase after IGF-I from cells that do not; (2) all cells that are induced to synthesize DNA by IGF-I have increased phosphorylation of MAP kinases, regardless of their ability to divide; (3) the same cell lines display a similar increase in cyclin A and B expression at early times after stimulation; and (4) cyclin levels and cyclin B-associated cdc2 kinase activity remain elevated at later times only in cells that undergo cell division. These results establish certain parameters of IGF-I-mediated mitogenesis and clearly separate the occurrence of DNA synthesis from cell division in certain situations.
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PMID:Molecular markers of IGF-I-mediated mitogenesis. 966 33

In budding yeast cells, the cytoskeletal polarization and depolarization events that shape the bud are triggered at specific times during the cell cycle by the cyclin-dependent kinase Cdc28p. Polarity establishment also requires the small GTPase Cdc42p and its exchange factor, Cdc24p, but the mechanism whereby Cdc28p induces Cdc42p-dependent polarization is unknown. Here we show that Cdc24p becomes phosphorylated in a cell cycle-dependent manner, triggered by Cdc28p. However, the role of Cdc28p is indirect, and the phosphorylation appears to be catalyzed by the p21-activated kinase family member Cla4p and also depends on Cdc42p and the scaffold protein Bem1p. Expression of GTP-Cdc42p, the product of Cdc24p-mediated GDP/GTP exchange, stimulated Cdc24p phosphorylation independent of cell cycle cues, raising the possibility that the phosphorylation is part of a feedback regulatory pathway. Bem1p binds directly to Cdc24p, to Cla4p, and to GTP-bound Cdc42p and can mediate complex formation between these proteins in vitro. We suggest that Bem1p acts to concentrate polarity establishment proteins at a discrete site, facilitating polarization and promoting Cdc24p phosphorylation at specific times during the cell cycle.
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PMID:Assembly of scaffold-mediated complexes containing Cdc42p, the exchange factor Cdc24p, and the effector Cla4p required for cell cycle-regulated phosphorylation of Cdc24p. 1111 54

Meiotic development (sporulation) in the yeast Saccharomyces cerevisiae is induced by nutritional deprivation. Smk1 is a meiosis-specific MAP kinase homolog that controls spore morphogenesis after the meiotic divisions have taken place. In this study, recessive mutants that suppress the sporulation defect of a smk1-2 temperature-sensitive hypomorph were isolated. The suppressors are partial function alleles of CDC25 and CYR1, which encode the Ras GDP/GTP exchange factor and adenyl cyclase, respectively, and MDS3, which encodes a kelch-domain protein previously implicated in Ras/cAMP signaling. Deletion of PMD1, which encodes a Mds3 paralog, also suppressed the smk1-2 phenotype, and a mds3-Delta pmd1-Delta double mutant was a more potent suppressor than either single mutant. The mds3-Delta, pmd1-Delta, and mds3-Delta pmd1-Delta mutants also exhibited mitotic Ras/cAMP phenotypes in the same rank order. The effect of Ras/cAMP pathway mutations on the smk1-2 phenotype required the presence of low levels of glucose. Ime2 is a meiosis-specific CDK-like kinase that is inhibited by low levels of glucose via its carboxy-terminal regulatory domain. IME2-DeltaC241, which removes the carboxy-terminal domain of Ime2, exacerbated the smk1-2 spore formation phenotype and prevented cyr1 mutations from suppressing smk1-2. Inhibition of Ime2 in meiotic cells shortly after Smk1 is expressed revealed that Ime2 promotes phosphorylation of Smk1's activation loop. These findings demonstrate that nutrients can negatively regulate Smk1 through the Ras/cAMP pathway and that Ime2 is a key activator of Smk1 signaling.
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PMID:The Ras/cAMP pathway and the CDK-like kinase Ime2 regulate the MAPK Smk1 and spore morphogenesis in Saccharomyces cerevisiae. 1908 57