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)

An antiserum that recognizes the heavy chain of Drosophila kinesin was used to isolate Drosophila cDNA clones. Immunoblot analysis of the proteolytic fragments of the protein produced by one of the cDNA clones has demonstrated that the cDNA clones encode the heavy chain of Drosophila kinesin. The in vitro-synthesized product of the largest cDNA comigrates with Drosophila kinesin heavy chain on NaDodSO4/polyacrylamide gels and binds to taxol-stabilized microtubules in the presence of the nonhydrolyzable analogue of ATP, 5'-adenylyl imidodiphosphate, but not in the presence of ATP or 0.1 M KCl. Analysis of the cDNA clones suggests that there is a single gene encoding kinesin heavy chain in Drosophila located at polytene chromosome position 53A. However, Southern hybridization analyses suggest the presence of related sequences in the Drosophila genome.
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PMID:Isolation and characterization of the gene encoding the heavy chain of Drosophila kinesin. 312 98

Neurons are highly polarized cells composed of dendrites, cell bodies, and long axons. Because of the lack of protein synthesis machinery in axons, materials required in axons and synapses have to be transported down the axons after synthesis in the cell body. Fast anterograde transport conveys different kinds of membranous organelles such as mitochondria and precursors of synaptic vesicles and axonal membranes, while organelles such as endosomes and autophagic prelysosomal organelles are conveyed retrogradely. Although kinesin and dynein have been identified as good candidates for microtubule-based anterograde and retrograde transporters, respectively, the existence of other motors for performing these complex axonal transports seems quite likely. Here we characterized a new member of the kinesin super-family, KIF3A (50-nm rod with globular head and tail), and found that it is localized in neurons, associated with membrane organelle fractions, and accumulates with anterogradely moving membrane organelles after ligation of peripheral nerves. Furthermore, native KIF3A (a complex of 80/85 KIF3A heavy chain and a 95-kD polypeptide) revealed microtubule gliding activity and baculovirus-expressed KIF3A heavy chain demonstrated microtubule plus end-directed (anterograde) motility in vitro. These findings strongly suggest that KIF3A is a new motor protein for the anterograde fast axonal transport.
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PMID:KIF3A is a new microtubule-based anterograde motor in the nerve axon. 751 68

Two microtubule-stimulated ATPases, cytoplasmic dynein, and kinesin, are believed to be responsible for the intracellular movement of membrane-bound organelles in opposite directions along microtubules. An unresolved component of this model is the mechanism by which cells regulate these two motors to direct various membrane-bound organelles to their proper locations. To determine if phosphorylation may play a role in the regulation of cytoplasmic dynein, the in vivo phosphorylation state of cytoplasmic dynein from two cellular pools was examined. The entire cellular pool of brain cytoplasmic dynein was metabolically labeled by the infusion of [32P]orthophosphate into the cerebrospinal fluid of rat brain ventricles. To characterize the phosphorylation of dynein associated with anterograde membrane-bound organelles, the optic nerve fast axonal transport system was used. Using a monoclonal antibody to the 74-kD polypeptide of brain cytoplasmic dynein, the native dynein complex was immunoprecipitated from the radiolabled tissue extracts. Autoradiographs of one and two dimensional gels showed labeling of nearly all of the polypeptide isoforms of cytoplasmic dynein from rat brain. These polypeptides are phosphorylated on serine residues. Comparison of the amount of 32P incorporated into the dynein polypeptides revealed differences in the phosphorylation of dynein polypeptides from the anterograde and the cellular pools. Most interestingly, the 530-kD heavy chain of dynein appears to be phosphorylated to a lesser extent in the anterograde pool than in the cellular pool. Since the anterograde pool contains inactive dynein, while the entire cellular pool contains both inactive and active dynein, these results are consistent with the hypothesis that phosphorylation regulates the functional activity of cytoplasmic dynein.
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PMID:Differential phosphorylation in vivo of cytoplasmic dynein associated with anterogradely moving organelles. 752 20

Kinesin is a microtubule (MT)-associated 'motor' molecule fundamental to organelle transport. Recently, various kinesin superfamily members (KIFs) have also been identified and suggested as being responsible for the transport of specific organelles. Kinesin is a heterotetramer composed of two heavy chains and two light chains. The heavy chains form two globular heads, a rod and a fan-like tail completed by the light chains. The globular head, which is composed of approximately 340 amino-terminal residues of the heavy chain, includes both ATP-binding and MT-binding domains, and its recombinant protein also has these properties. To improve the understanding of the mechanism of force generation by an MT-based molecular motor, kinesin, we report here the three-dimensional structure of the complex of a recombinant kinesin head and MTs, as revealed by helical reconstruction from cryo-electron micrographs. A kinesin head is a globular teardrop-like structure binding to the ridge of one protofilament of MTs. We have determined the polarity of the structure of the complex of MTs and the kinesin head in relation to MT polarity.
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PMID:Three-dimensional structure of the kinesin head-microtubule complex. 761 26

The N-terminal residues of the two heavy chains of the motor enzyme kinesin form two globular "heads"; the heads are attached to a "rod" domain which is a two-stranded alpha-helical coiled-coil. Interaction between the heads is thought to be important to kinesin function. The rod may not be necessary for head-head interactions because a heavy chain N-terminal fragment containing only residues from the head and adjacent region forms dimers (Huang, T.-G., Suhan, J., and Hackney, D. D. (1994) J. Biol. Chem. 269, 16502-16507). However, the nature and stability of the subunit-subunit interactions in such derivatives are unclear. To examine the physical properties of heavy chain interaction in and near the head domains, we characterized the self-association behavior of two dimeric kinesin derivatives predicted (Lupas, A., van Dyke, M., and Stock, J. (1991) Science 252, 1162-1164) to lack the rod. Derivative K448-BIO contains the 448 N-terminal residues of Drosophila kinesin heavy chain fused at the C terminus to a 2-residue linker and a C-terminal fragment from Escherichia coli biotin carboxyl carrier protein; derivative K448-L is the same except that it lacks the biotin carboxyl carrier protein fragment. Both derivatives expressed in insect cells display microtubule-stimulated ATPase activity; K448-BIO also displays microtubule motility. Equilibrium sedimentation and gel filtration indicate that purified K448-BIO and K448-L at 0.02-0.4 mg/ml form homogeneous solutions of homodimers with no detectable formation of monomers or higher order oligomers. Derivative self-association is non-covalent but extremely stable with an association constant > or = 2 x 10(8) M-1. Stable subunit-subunit association induced by structures in and near the kinesin heads may be necessary for full mechanochemical function.
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PMID:Subunit interactions in dimeric kinesin heavy chain derivatives that lack the kinesin rod. 787 39

The distribution of membrane-bound organelles was studied in cultured hippocampal neurons after antisense oligonucleotide suppression of the kinesin-heavy chain (KHC). We observed reduced 3,3'-dihexyloxacarbocyanine iodide (DiOC6(3)) fluorescent staining in neurites and growth cones. In astrocytes, KHC suppression results in the disappearance of the DiOC6(3)-positive reticular network from the cell periphery, and a parallel accumulation of label within the cell center. On the other hand, mitochondria microtubules and microfilaments display a distribution that closely resembles that observed in control cells. KHC suppression of neurons and astrocytes completely inhibited the Brefeldin A-induced spreading and tubulation of the Golgi-associated structure enriched in mannose-6-phosphate receptors. In addition, KHC suppression prevents the low pH-induced anterograde redistribution of late endocytic structures. Taken collectively, these observations suggest that in living neurons, kinesin mediates the anterograde transport of tubulovesicular structures originated in the central vacuolar system (e.g., the endoplasmic reticulum) and that the regulation of kinesin-membrane interactions may be of key importance for determining the intracellular distribution of selected organelles.
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PMID:Kinesin-mediated organelle translocation revealed by specific cellular manipulations. 796 67

Physarum polycephalum, a low eukaryote ameba provides an attractive system for studying contractile proteins. In this work, we have identified a kinesin-like protein in the plasmodium of Physarum polycephalum by western blotting, using monoclonal antibody against kinesin (bovine brain). The molecular weight of the polypeptide which immunologically cross-reacts with kinesin from bovine brain is about 137kd. It suggests that the 137kd polypeptide is the heavy chain of the kinesin in Physarum polycephalum.
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PMID:[Immunochemical identification of kinesin in Physarum polycephalum]. 807 64

We describe a general strategy for cloning mammalian genes whose downregulation results in a selectable phenotype. This strategy is based on expression selection of genetic suppressor elements (GSEs), cDNA fragments encoding either specific peptides that act as dominant inhibitors of protein function or antisense RNA segments that efficiently inhibit gene expression. Since GSEs counteract the gene from which they are derived, they can be used as dominant selectable markers for the phenotype associated with downregulation of the corresponding gene. A retroviral library containing random fragments of normalized (uniform abundance) cDNA expressed in mouse NIH 3T3 cells was used to select for GSEs inducing resistance to the anticancer drug etoposide. Three GSEs were isolated, two of which are derived from unknown genes and the third encodes antisense RNA for the heavy chain of a motor protein kinesin. The kinesin-derived GSE induces resistance to several DNA-damaging drugs and immortalizes senescent mouse embryo fibroblasts, indicating that kinesin is involved in the mechanisms of drug sensitivity and in vitro senescence. Expression of the human kinesin heavy-chain gene was decreased in four of four etoposide-resistant HeLa cell lines, derived by conventional drug selection, indicating that downregulation of kinesin represents a natural mechanism of drug resistance in mammalian cells.
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PMID:Cloning mammalian genes by expression selection of genetic suppressor elements: association of kinesin with drug resistance and cell immortalization. 817 Sep 81

Kinesin heavy chain and kinesin-related polypeptides (KRPs) comprise a family of motor proteins with diverse intracellular transport functions. Using pan-kinesin peptide antibodies that react with these proteins, we have previously purified from sea urchin eggs a trimeric microtubule-binding and bundling protein, KRP (85/95) (ref. 8) comprising subunits of M(r) 115,000 (115K), 95K and 85K. We report here that kinesin-related genes encode the 85K and 95K subunits, and that the protein can be immunoprecipitated from cytosol as a trimeric complex using an 85K monoclonal antibody. We also find that purified KRP(85/95) directs movements towards the 'plus' ends of microtubules. To our knowledge, this protein is the first kinesin-related motor to be purified from its natural host cell in a native multimeric state.
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PMID:Novel heterotrimeric kinesin-related protein purified from sea urchin eggs. 823 86

Sea urchin kinesin is a plus end-directed microtubule-based motor consisting of two heavy chains and two light chains and is proposed to be responsible (a) for the transport of membranous organelles along microtubules in sea urchin mitotic spindles (Wright, B. D., Henson, J. H., Wedaman, K. P., Willy, P. J., Morand, J. N., and Scholey, J. M. (1991) J. Cell Biol. 113, 817-833) and (b) for the radial dispersion of endoplasmic reticulum and endosomal membranes in non-mitotic cultured coelomocytes (Henson, J. H., Nesbitt, D., Wright, B. D., and Scholey, J. M. (1992) J. Cell Sci. 103, 309-320). We report here that sea urchin kinesin is indeed able to bind in a concentration-dependent and saturable manner to microsomal membranes isolated from sea urchin eggs in the presence of MgATP. The kinesin light chains may not be essential for membrane binding since kinesin containing negligible amounts of light chains binds as well as kinesin containing stoichiometric amounts of light chains. Finally, we propose that kinesin binds to membranes with the carboxyl-terminal domain of the heavy chain (amino acid residues 858-1031) since the bacterially expressed and then isolated stalk-tail fragment of kinesin heavy chain, in contrast to the stalk fragment, is able (a) to bind membranes in a concentration-dependent and saturable manner and (b) to compete with native kinesin for membrane binding. Our results support the hypothesis that the carboxyl-terminal domains of the heavy chains attach kinesin molecules to their membranous cargo in mitotic and interphase sea urchin cells.
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PMID:The carboxyl-terminal domain of kinesin heavy chain is important for membrane binding. 828 13


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