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)

While cyclin-dependent kinase 5 (Cdk5) is widely distributed in mammalian tissues and in cultured cell lines, Cdk5-associated kinase activity has been demonstrated only in mammalian brains. An active form of Cdk5, called neuronal cdc2-like kinase (Nclk) has been purified from mammalian brain and shown to be a heterodimer of Cdk5 and a 25 kDa protein, which is derived proteolytically from a 35 kDa brain and neuron-specific protein. The protein is essential for the kinase activity of Cdk5 and is therefore designated neuronal Cdk5 activator, p25/35Nck5a. Nclk appears to have important neuronal functions. The changes in Cdk5 and Nck5a expression appear to correlate with the terminal differentiation of neurons of the mouse embryonic brain. Transfection of cultured cortical neurons with dominant negative cdk5 mutants or Nck5a antisense DNA may reduce neurite growth, suggesting that Nclk plays an active role in neuron differentiation. A number of cytoskeletal proteins including neurofilament proteins, the neuron-specific microtubule associated protein tau, and the actin binding protein caldesmon are in vitro substrates of Nclk. Although Nck5a has cyclin-like activity, it shows minimal amino acid sequence identity to members of cyclin family proteins. The mechanism of activation of Cdk5 by Nck5a differs from that of cyclin activation of Cdks in that full Cdk5 kinase activity can be achieved in the absence of phosphorylation of Cdk5. An isoform of Nck5a, a 39 kDa protein has been cloned and shown to share extensive amino acid identity and the mechanism of Cdk5 activation with Nck5a. These proteins may represent a subfamily of Cdk activators distinct from cyclins.
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PMID:Cyclin-dependent kinase 5 (Cdk5) and neuron-specific Cdk5 activators. 955 97

In Alzheimer disease brain the microtubule associated protein (MAP) tau is abnormally hyperphosphorylated. The role of protein phosphatases (PP) in the regulation of phosphorylation of tau was studied in undifferentiated SY5Y cells. In cells treated with 10 nM okadaic acid (OA), a PP-2A/PP-1 inhibitor, the PP-1 and -2A activities decreased by 60% and 100% respectively and the activities of MAPKs, cdc2 kinase and cdk5, but not of GSK-3, increased. OA increased the phosphorylation of tau at Thr-231/Ser-235 and Ser-3961404, but not at Ser-262/356 or Ser-199/202. An increase in tyrosinated/detyrosinated tubulin ratio, a decrease in the microtubule binding activities of tau, MAP1b and MAP2, and cell death were observed. Treatment with 1 microm taxol partially inhibited the cell death. These data suggest (1) that OA induced hyperphosphorylation of tau is probably the result of activated MAPK and cdks in addition to decreased PP-2A and PP-1 activities and (2) that in SY5Y cells the OA induced cell death is associated with a decrease in stable microtubules.
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PMID:The regulation of phosphorylation of tau in SY5Y neuroblastoma cells: the role of protein phosphatases. 959 18

Axonal degeneration has been described as the pathological hallmark of peripheral neuropathies induced by DEDTC. In addition, axonal damage has also been observed in the brain of mice treated daily with DEDTC along postnatal development, though with this experimental model there was observed to be axonal recovery after treatment, during the adulthood. To focus on this axonal dynamic activity, damage-recovery, a key axonal protein, the microtubule associated protein tau, was analyzed in this DEDTC model. Tau is a phosphoprotein and its dynamic site-specific phosphorylation is essential for its proper function; in fact, high levels are correlated with cell dysfunction. Furthermore, the levels of tau phosphorylation are associated with dynamic microtubules during periods of high plasticity. Thus, phosphorylated tau at two sites of phosphorylation, Ser(199) and Ser(396), were evaluated during the second week of postnatal development and throughout adulthood. The results obtained by Western blot made it evident that the levels of p-tau Ser(199) and p-tau Ser(396) were higher in treated mice than in controls. Interestingly, by immunohistochemistry there was shown to be an increase in p-tau-immunolabeling in neuronal soma together with axonal tract alterations in treated animals with respect to controls, and the analyses of GSK3 beta and cdk5 revealed an increase in its activity in DEDTC-treated animals. Nevertheless, in the adult a general decline in p-tau was observed together with a rescue of axonal tract. All these data support the idea that the axonal damage induced by DEDTC treatment along postnatal development is followed by an axonal rescue during adulthood.
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PMID:Tau hyperphosphorylation and axonal damage induced by N,N-diethyldithiocarbamate (DEDTC) treatment along late postnatal development is followed by a rescue during adulthood. 1990 81

Cytokinesis begins in anaphase with the formation of the central spindle. PRC1 is a microtubule associated protein that plays an essential role in central spindle formation by crosslinking antiparallel microtubules. We have identified PRC1 as a novel binding partner for p27Kip1 (p27). p27 is a cyclin-CDK inhibitor that causes cell cycle arrest in G1. However, p27 has also been involved in the regulation of G2/M progression and cytokinesis, as well as of other cellular processes, including actin and microtubule cytoskeleton dynamics. We found that p27 interferes with the ability of PRC1 to bind to microtubules, without affecting PRC1 dimerization or its capacity to interact with other partners such as KIF4. In this way, p27 inhibited microtubule bundling by PRC1 in vitro and prevented the extensive microtubule bundling phenotype caused by PRC1 overexpression in cells in culture. Finally, co-expression of p27 or a p27 mutant that does not bind cyclin-CDKs inhibited multinucleation induced by PRC1 overexpression. Together, our results suggest that p27 may participate in the regulation of mitotic progression in a CDK-independent manner by modulating PRC1 activity.
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PMID:p27Kip1 regulates the microtubule bundling activity of PRC1. 3032 4