Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.4.4 (kinesin)
 5,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kinesin, a plus-end-directed microtubule motor protein, functions in concert with accessory factors that have been shown to regulate enzyme activity and may also provide cargo specificity. This report identifies teh 79-kDa kinesin-associated phosphoprotein as a phosphoisoform of kinesin light chain. Increased phosphorylation of this light chain isoform is sufficient to account for the increase in kinesin-mediated microtubule-gliding activity. Additionally, it was found that the degree of phosphorylation of this isoform is regulated by a 100-kDa kinase and 150-kDa type 1 phosphatase. Both the kinesin light chain kinase and phosphatase co-purify with the kinesin heavy chain, suggesting that kinesin exists in a large complex capable of self-regulation.
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PMID:Phosphotransferases associated with the regulation of kinesin motor activity. 931 51

Rapid organelle transport is required for process growth and establishment of specialized structures during neuronal development. Furthermore, maintenance of mature neuronal architecture and function depends on the proper delivery of materials to specialized domains within axons, such as nodes of Ranvier and synaptic terminals. Kinesin is the most abundant member of the kinesin superfamily of microtubule-based motors. Kinesins are responsible for anterograde transport of an assortment of membrane-bound organelles in all cell types. Kinesin is enriched in neurons, but relatively little is known about the developmental regulation of its expression, localization, and function in nervous tissue. By examining kinesin expression in developing brain and in cultures of cortical neurons, we found that kinesin is enriched in elongating neurites, including their growing tips, the growth cones. To gain understanding of mechanisms that underlie the delivery of proteins to specific cellular subcompartments, we focused on studying modifications on kinesin that lead to its dissociation from membranes. Since kinesin is a phosphoprotein in vivo, we evaluated the correlation between kinesin phosphorylation and its membrane association and identified a number of kinases which phosphorylate kinesin and alter its function.
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PMID:Regulation of kinesin: implications for neuronal development. 1175 52

The motility of cilia and flagella is powered by dynein ATPases associated with outer doublet microtubules. However, a flagellar kinesin-like protein that may function as a motor associates with the central pair complex. We determined that Chlamydomonas reinhardtii central pair kinesin Klp1 is a phosphoprotein and, like conventional kinesins, binds to microtubules in vitro in the presence of adenosine 5'-[beta,gamma-imido]triphosphate, but not ATP. To characterize the function of Klp1, we generated RNA interference expression constructs that reduce in vivo flagellar Klp1 levels. Klp1 knockdown cells have flagella that either beat very slowly or are paralyzed. EM image averages show disruption of two structures associated with the C2 central pair microtubule, C2b and C2c. Greatest density is lost from part of projection C2c, which is in a position to interact with doublet-associated radial spokes. Klp1 therefore retains properties of a motor protein and is essential for normal flagellar motility. We hypothesize that Klp1 acts as a conformational switch to signal spoke-dependent control of dynein activity.
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PMID:Regulation of flagellar dynein activity by a central pair kinesin. 1557 40

Inositol 1,4,5-trisphosphate (IP(3)) is a second messenger that induces the release of Ca(2+) from the endoplasmic reticulum (ER). The IP(3) receptor (IP(3)R) was discovered as a developmentally regulated glyco-phosphoprotein, P400, that was missing in strains of mutant mice. IP(3)R can allosterically and dynamically change its form in a reversible manner. The crystal structures of the IP(3)-binding core and N-terminal suppressor sequence of IP(3)R have been identified. An IP(3) indicator (known as IP(3)R-based IP(3) sensor) was developed from the IP(3)-binding core. The IP(3)-binding core's affinity to IP(3) is very similar among the three isoforms of IP(3)R; instead, the N-terminal IP(3) binding suppressor region is responsible for isoform-specific IP(3)-binding affinity tuning. Various pathways for the trafficking of IP(3)R have been identified; for example, the ER forms a meshwork upon which IP(3)R moves by lateral diffusion, and vesicular ER subcompartments containing IP(3)R move rapidly along microtubles using a kinesin motor. Furthermore, IP(3)R mRNA within mRNA granules also moves along microtubules. IP(3)Rs are involved in exocrine secretion. ERp44 works as a redox sensor in the ER and regulates IP(3)R1 activity. IP(3) has been found to release Ca(2+), but it also releases IRBIT (IP(3)R-binding protein released with IP(3)). IRBIT is a pseudo-ligand for IP(3) that regulates the frequency and amplitude of Ca(2+) oscillations through IP(3)R. IRBIT binds to pancreas-type Na, bicarbonate co-transporter 1, which is important for acid-base balance. The presence of many kinds of binding partners, like homer, protein 4.1N, huntingtin-associated protein-1A, protein phosphatases (PPI and PP2A), RACK1, ankyrin, chromogranin, carbonic anhydrase-related protein, IRBIT, Na,K-ATPase, and ERp44, suggest that IP(3)Rs form a macro signal complex and function as a center for signaling cascades. The structure of IP(3)R1, as revealed by cryoelectron microscopy, fits closely with these molecules.
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PMID:IP3 receptor/Ca2+ channel: from discovery to new signaling concepts. 1769 45

As the ortholog of human SR protein kinase 1 in fission yeast Schizosaccharomyces pombe, Dsk1 specifically phosphorylates SR proteins (serine/arginine-rich proteins) and promotes splicing of nonconsensus introns. The SRPK (SR protein-specific kinase) family performs highly conserved functions in eukaryotic cells including cell proliferation, differentiation, development, and apoptosis. Although Dsk1 was originally identified as a mitotic regulator, its specific targets involved in cell cycle have yet been unexplored. In this study, using a phosphoproteomics approach, we examined differential protein phosphorylation between wild-type cells and dsk1-deletion mutants. We found reduced phosphorylation of 149 peptides corresponding to 133 proteins in the dsk1-null cells. These proteins are involved in various cellular processes, including cytoskeleton organization and signal transduction, and specifically enriched in multiple steps of cell cycle control. Further, targeted MS analyses and in vitro biochemical assays established Cdr2 protein kinase and kinesin motor Klp9 as novel substrates of Dsk1, which function in cell size control for mitotic entry and in chromosome segregation for mitotic exit, respectively. The phosphoprotein networks mediated by Dsk1 reveal, for the first time, the molecular links connecting Dsk1 to mitotic phase transition, sister-chromatid segregation, and cytokinesis, providing further evidence of Dsk1's diverse influence on cell cycle progression and regulation.
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PMID:Phosphoproteomics Reveals Novel Targets and Phosphoprotein Networks in Cell Cycle Mediated by Dsk1 Kinase. 3206 75