Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.4.4 (kinesin)
5,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, we reported the construction of a cDNA library encoding a heterogeneous population of polyadenylated mRNAs present in the squid giant axon. The nucleic acid sequencing of several randomly selected clones led to the identification of cDNAs encoding beta-actin and beta-tubulin, two relatively abundant axonal mRNA species. To continue characterization of this unique mRNA population, the axonal cDNA library was screened with a cDNA probe encoding the carboxy terminus of the squid kinesin heavy chain. The sequencing of several positive clones unambiguously identified axonal kinesin cDNA clones. The axonal localization of kinesin mRNA was subsequently verified by in situ hybridization histochemistry. In addition, the presence of kinesin RNA sequences in the axoplasmic polyribosome fraction was demonstrated using PCR methodology. In contrast to these findings, mRNA encoding the squid sodium channel was not detected in axoplasmic RNA, although these sequences were relatively abundant in the giant fiber lobe. Taken together, these findings demonstrate that kinesin mRNA is a component of a select group of mRNAs present in the squid giant axon, and suggest that kinesin may be synthesized locally in this model invertebrate motor neuron.
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PMID:Kinesin mRNA is present in the squid giant axon. 820 22

Hepatocyte growth factor (HGF) and epidermal growth factor (EGF) are known to stimulate the locomotion of epithelial cells in culture. However, the molecular mechanisms which mediate these important changes are poorly understood. Here we have determined the effects of HGF and EGF on hepatocyte morphology, cytoskeletal organization, and the expression of molecular motor-encoding genes. Primary cultures of hepatocytes were treated with 10 ng/ml of HGF or EGF and observed with phase and fluorescence microscopy at 10, 24, and 48 h after treatment. We found that, over time, treated cells spread and became elongated after 24 h of treatment while forming long processes with dramatic alterations in the microtubule and actin cytoskeletons by 48 h. Quantitative Northern blot analysis was performed to measure expression of cytoskeletal-(beta-actin, alpha-tubulin) and molecular motor-(dynein, kinesin, and myosin I alpha and II) encoding genes which may contribute to this change in form. We observed the highest increase in levels of expression for myosin II (3.3-fold), kinesin (2.7-fold), myosin I alpha (2.2-fold), and alpha-tubulin (1.9-fold) after only 2 h of treatment with HGF. In contrast, EGF upregulated the expression of myosin I alpha (2.4-fold), kinesin (1.5-fold), and dynein (1.5-fold) at 10 h. The expression of the beta-actin gene remained constant in HGF-treated cells, while EGF induced a slight upregulation after 10 h of treatment. These results show for the first time that a selective upregulation of molecular motor-encoding genes correlates with alterations in cell shape and motility induced by HGF and EGF.
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PMID:Upregulation of molecular motor-encoding genes during hepatocyte growth factor- and epidermal growth factor-induced cell motility. 865 96

Previously, we reported that the squid giant axon contains a heterogeneous population of mRNAs that includes beta-actin, beta-tubulin, kinesin, neurofilament proteins, and enolase. To define the absolute levels and relative distribution of these mRNAs, we have used competitive reverse transcription-PCR to quantify the levels of five mRNAs present in the giant axon and giant fiber lobe (GFL), the location of the parental cell soma. In the GFL, the number of transcripts for these mRNAs varied over a fourfold range, with beta-tubulin being the most abundant mRNA species (1.25 x 10(9) molecules per GFL). Based on transcript number, the rank order of mRNA levels in the GFL was beta-tubulin > beta-actin > kinesin > enolase > microtubule-associated protein (MAP) H1. In contrast, kinesin mRNA was most abundant in the axon (4.1 x 10(7) molecules per axon) with individual mRNA levels varying 15-fold. The rank order of mRNA levels in the axon was kinesin > beta-tubulin > MAP H1 > beta-actin > enolase. The relative abundance of the mRNA species in the axon did not correlate with the size of the transcript, nor was it directly related to their corresponding levels in the GFL. Taken together, these findings confirm that significant amounts of mRNA are present in the giant axon and suggest that specific mRNAs are differentially transported into the axonal domain.
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PMID:Differential compartmentalization of mRNAs in squid giant axon. 886 84

The critical role of microtubules in vectorial delivery of post-Golgi carrier vesicles to the apical cell surface has been established for various polarized epithelial cell types. In the present study we used secretory granules of the rat and chicken pancreas, termed zymogen granules, as model system for apically bound post-Golgi carrier vesicles that underlie the regulated exocytotic pathway. We found that targeting of zymogen granules to the apical cell surface requires an intact microtubule system which contains its colchicine-resistant organizing center and, thus, the microtubular minus ends close to the apical membrane domain. Purified zymogen granules and their membranes were found to be associated with cytoplasmic dynein intermediate and heavy chain and to contain the major components of the dynein activator complex, dynactin, i.e. p150Glued, p62, p50, Arp1, and beta-actin. Kinesin heavy chain and the kinesin receptor, 160 kD kinectin, were not detected as components of zymogen granules. Immunofluorescence staining showed a zymogen granule-like distribution for dynein and dynactin (p150Glued, p62, p50, Arpl) in the apical cytoplasm, whereas kinesin and kinectin were largely concentrated in the basal half of the cells in a pattern similar to the distribution of calreticulin, a component of the endoplasmic reticulum. Secretory granules of non-polarized chromaffin cells of the bovine adrenal medulla, that are assumed to underlie microtubular plus end targeting from the Golgi apparatus to the cell periphery, were not found to be associated with dynein or dynactin. To our knowledge, this is the first demonstration of major components of the dynein-dynactin complex associated with the membrane of a biochemically and functionally well-defined organelle which is considered to underlie a vectorial minus end-driven microtubular transport critically involved in precise delivery of digestive enzymes to the apically located acinar lumen.
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PMID:Cytoplasmic dynein and dynactin as likely candidates for microtubule-dependent apical targeting of pancreatic zymogen granules. 1035 Feb 15

The inhibition of kinesin Eg5 by small molecules such as monastrol is currently evaluated as an approach to develop a novel class of antiproliferative drugs for the treatment of malignant tumours. Therefore, we studied the effects of the new monastrol analogues enastron, dimethylenastron and vasastrol VS-83 on the proliferation of human glioblastoma cells in the kinetic crystal violet assay. Compared to monastrol, the new cell cycle specific compounds showed an at least one order of magnitude higher anti proliferative activity against U-87 MG, U-118 MG, and U-373 MG glioblastoma cells. The compounds were neither inactivated by hydrolysis nor by binding to serum proteins. Moreover, we demonstrated the characteristic monoaster formation after incubation of cells with the new compounds by confocal laser scanning microscopy. We also showed that the arrangement of beta-actin and tubulin, vital components of the cyto-skeleton of mitotic and quiescent cells, were not affected by the new compounds. Due to the necessity of overcoming the blood-brain barrier in the treatment of brain tumours, we investigated if the new monastrol analogues are modulators or substrates of the p-glycoprotein (p-gp) 170 by a flow cytometric calcein-AM efflux assay. The tested compounds showed no modulating effects on the p-gp function. With respect to the treatment of primary and secondary CNS tumours, the results of our experiments suggest that the new monastrol analogues represent an interesting class of potential anticancer drugs, predicted to be less neurotoxic in comparison to classical tubulin inhibitors.
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PMID:Inhibitors of kinesin Eg5: antiproliferative activity of monastrol analogues against human glioblastoma cells. 1670 23

The regulation of mRNA transport is a fundamental process for cytoplasmic sorting of transcripts and spatially controlled translational derepression once properly localized. There is growing evidence that translation is locally modulated as a result of specific synaptic inputs. However, the underlying molecular mechanisms that regulate this translational process are just emerging. We show that KIS, a serine/threonine kinase functionally related to microtubule dynamics and axon development, interacts with three proteins found in RNA granules: KIF3A, NonO, and eEF1A. KIS localizes to RNA granules and colocalizes with the KIF3A kinesin and the beta-actin mRNA in cultured cortical neurons. In addition, KIS is found associated with KIF3A and 10 RNP-transported mRNAs in brain extracts. The results of knockdown experiments indicate that KIS is required for normal neurite outgrowth. More important, the kinase activity of KIS stimulates 3' untranslated region-dependent local translation in neuritic projections. We propose that KIS is a component of the molecular device that modulates translation in RNA-transporting granules as a result of local signals.
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PMID:Protein kinase KIS localizes to RNA granules and enhances local translation. 1901 37

Periaxoplasmic ribosomal plaques (PARPs) are systematically recurring ribosome-containing structural domains located in the F-actin-rich periphery of axoplasm in myelinated fibers. In contrast, endoaxoplasmic ribosomal plaques (EARPs) are small, oval-shaped ribosomal aggregate structures randomly dispersed within the axoplasm of unmyelinated squid giant axons. Ribosomes are attached to a superficial plaque-like structural matrix, which "caps" the domain at the outer cortical margin and appears fragmented in subcortical axoplasm. As such, the matrix represents a novel hallmark of PARP domains. Molecular markers concentrated in PARP domains include beta-actin mRNA, ZBP-1, SRP54, myosin Va and kinesin II molecular motor proteins. Rapid axoplasmic transport of microinjected heterologous radiolabeled BC1 RNA to putative PARP domains, mediated pari passu by microtubule- and F-actin-dependent systems, suggests that translation machinery, anchored by the matrix could provide targeted destinations for RNA trafficking. As distributed local centers of protein synthesis along axons, PARPs are likely to share modes of expression in common with other translational subdomains in neurons.
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PMID:Organized ribosome-containing structural domains in axons. 1913 68

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