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

Attention has recently been paid to the role of microtubules in the transduction of growth signals, which has recently been establishing as a molecular function of microtubule cytoskeletons. The analysis of pathways in the signal transductions which are initiated by the activation of tyrosine-specific phosphorylation of growth factor receptors now seems to come to deal with events deeper inside the cell. It was recently found that MAP kinase which preferentially phosphorylates microtubule-associated protein 2 is largely activated at the G0/G1 transition by any of various growth stimuli. The kinase is also activated at the G2/M transition in the downstream of MPF (cdc2 kinase). Furthermore, it was suggested that a GTP-binding protein (51-kD protein) in the centrosome plays a role in the microtubule signalling at the onset of mitosis. This minireview discusses possible signalling pathway from the activation of tyrosine-specific protein kinase of the growth factor receptor to the initiation of mitosis.
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PMID:[Role of microtubule cytoskeletons in the transduction of growth signals]. 165 96

Cdc42p, a Rho-related GTP-binding protein, regulates cytoskeletal polarization and rearrangements in eukaryotic cells. In yeast, Gic1p and Gic2p are effectors of Cdc42p involved in actin polarization at bud emergence. Gic2p is expressed in a cell cycle-dependent manner and rapidly disappears shortly after bud emergence concomitant with the activation of the G1 cyclin-dependent kinase Cdc28p-Clnp. Here we have shown that the rapid disappearance of Gic2p results from ubiquitin-dependent proteolysis. Biochemical and genetic evidence demonstrates that degradation of Gic2p required the Skp1-cullin-F-box protein complex (SCF) components Cdc34p, Cdc53p, Skp1p and Grr1p, but not Cdc4p. Phosphorylation of several C-terminal sites of Gic2p served as part of the recognition signal for ubiquitination. In addition, binding of Gic2p to Cdc42p was a prerequisite for degradation, suggesting that specifically the active form of Gic2p is targeted for destruction. Finally, our data indicate that degradation of Gic2p may be part of a mechanism which restricts cytoskeletal polarization in the G1 phase of the cell cycle.
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PMID:The Cdc42p effector Gic2p is targeted for ubiquitin-dependent degradation by the SCFGrr1 complex. 973 14

Rat hepatocytes adherent to a rigid film of type I collagen will spread and enter S phase, while those attached to collagen gel or a dried collagen substrate remain round and quiescent. The current studies were initiated to determine the mechanism by which these different substrates differentially influence cell cycle progression. Cyclin D1 mRNA and protein expression and associated kinase activity was low on dried collagen relative to collagen film. In contrast, cyclin E and cdk2 protein levels were similar on the two substrates. Although cyclin E and cdk2 were present, cells on dried collagen lacked cdk2 kinase activity. p27 protein levels did not differ between dried collagen and film, but more p27 was associated with cdk2 in cells on dried collagen than those on collagen film. Cyclin D1 expression on collagen film was inhibited by cytochalasin D and exoenzyme C3, suggesting a role for the GTP-binding protein, Rho, in regulating cyclin D1 expression. Cyclin D1 over-expression induced hepatocytes into S phase in the absence of cell shape change on dried collagen or collagen gel. These results demonstrate a novel, substrate-dependent mechanism for cyclin D1 expression in hepatocytes, and also demonstrate that cyclin D1 over-expression allows shape-independent S phase entry.
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PMID:Regulation of the hepatocyte cell cycle by type I collagen matrix: role of cyclin D1. 1044 91

The receptor-generated signals that are responsible for driving the cell cycle are incompletely characterised in mammalian cells. It is clear, however, that the cellular messenger systems that stimulate DNA synthesis and mitosis are separable. These are interwoven with biochemical checkpoints that ensure that processes, such as chromosomal replication and microtubule attachment to duplicated chromosomes, are complete before the following phase of the cell cycle is initiated. In some cells, activation of DNA synthesis by factors such as LPA and serum has been shown to require the GTP-binding protein G(i). We have found that G(i) plays an additional role in mitosis activated by both 7-transmembrane receptors and tyrosine kinase receptors, and that this involves the translocation of the alpha-subunit of G(i) (G(ialpha)) to the nucleus. Here we show by confocal microscopy that G(ialpha)migrates to the nucleus near the onset of mitosis in serum-activated Swiss 3T3 cells and binds to the kinetochore region of replicated chromosomes. Inhibition of G(i) function with pertussis toxin had no effect on the induction of DNA synthesis by serum, but cell proliferation was inhibited. Flow cytometric analysis showed that this resulted from retardation of the transition through mitosis and into G(1). Additionally, pertussis toxin impaired the activity of p34(cdc2), a cyclin-dependent kinase involved in the transition from M-phase to G(1), but not the S-phase cyclin, cyclin E. These data show that the G-protein G(i) has a key role in the regulation of mitosis in fibroblasts.
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PMID:The GTP-binding protein G(ialpha) translocates to kinetochores and regulates the M-G(1) cell cycle transition of Swiss 3T3 cells. 1070 22

The YWK-II cDNA, RSD-2, encoding a sperm membrane protein was isolated from a rat testis cDNA expression library. Using the RSD-2 insert in combination with rapid amplification of cDNA ends (RACE), the corresponding human gene was isolated from a human testis cDNA expression library. The human testis cDNA, HSD-2, is 3654 bp in length and contains an open reading frame of 763 codons. Hydropathicity analysis showed that the deduced polypeptide is a single strand transmembrane protein. The deduced polypeptide has partial homology with the amyloid precursor protein (APP) and high homology with the amyloid precursor homologue, APLP2/APPH. The YWK-II gene was mapped and assigned to human chromosome locus: 11q24-25. Northern blotting of various human tissue RNAs using the HSD-2 cDNA as a probe showed that the gene is transcribed ubiquitously. The cytoplasmic domain of HSD-2 was expressed in Escherichia coli. In-vitro studies showed that the recombinant polypeptide bound to a GTP-binding protein (G(o)) and was phosphorylated by protein kinase C and cdc2 kinase. In mammalian F11 cells, the recombinant polypeptide was found to be coupled to G(o). Thus, the YWK-II component has the characteristics of a G(o)-coupled receptor and may be involved in G(o)-mediated signal transduction pathway. Protein kinase C and cdc2 kinase may regulate this pathway in spermatozoa by phosphorylating the cytoplasmic domain of the YWK-II component.
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PMID:Expression and characterization of the human YWK-II gene, encoding a sperm membrane protein related to the alzheimer betaA4-amyloid precursorprotein. 1110 89

Nucleolar GTP-binding protein (NGP-1) is overexpressed in various cancers and proliferating cells, but the functional significance remains unknown. In this study, we show that NGP-1 promotes G1 to S phase transition of cells by enhancing CDK inhibitor p21(Cip-1/Waf1) expression through p53. In addition, our results suggest that activation of the cyclin D1-CDK4 complex by NGP-1 via maintaining the stoichiometry between cyclin D1-CDK4 complex and p21 resulted in hyperphosphorylation of retinoblastoma protein at serine 780 (p-RB(Ser-780)) followed by the up-regulation of E2F1 target genes required to promote G1 to S phase transition. Furthermore, our data suggest that ribosomal protein RPL23A interacts with NGP-1 and abolishes NGP-1-induced p53 activity by enhancing Mdm2-mediated p53 polyubiquitination. Finally, reduction of p-RB(Ser-780) levels and E2F1 target gene expression upon ectopic expression of RPL23a resulted in arrest at the G1 phase of the cell cycle. Collectively, this investigation provides evidence that NGP-1 promotes cell cycle progression through the activation of the p53/p21(Cip-1/Waf1) pathway.
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PMID:Nucleolar GTP-binding Protein-1 (NGP-1) Promotes G1 to S Phase Transition by Activating Cyclin-dependent Kinase Inhibitor p21 Cip1/Waf1. 2620 95