By Toshio Ohshima (auth.), Li-Huei Tsai, Nancy Y. Ip (eds.)
Cyclin established Kinase 5 offers a finished and up to date choice of reports at the discovery, signaling mechanisms and features of Cdk5, in addition to the aptitude implication of Cdk5 within the remedy of neurodegenerative ailments. because the id of this exact member of the Cdk kin, Cdk5 has emerged as some of the most very important sign transduction mediators within the improvement, upkeep and fine-tuning of neuronal features and networking. extra experiences have printed that Cdk5 can be linked to the rules of neuronal survival in the course of improvement in addition to in neurodegenerative ailments. those observations point out that specified keep watch over of Cdk5 is key for the law of neuronal survival. The pivotal function that Cdk5 looks to play in either the legislation of neuronal survival and synaptic features therefore increases the fascinating risk that Cdk5 inhibitors can have healing strength for the therapy of a couple of neurodegenerative diseases.
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Extra info for Cyclin Dependent Kinase 5 (Cdk5)
When coexpressed with GSK3b and Cdk5/p35, CRMP2 was more phosphorylated and the intensity of upper band relatively increased, thereby indicating phosphorylation at additional sites. No phosphorylation and band shift were observed in the co-expression of CRMP2S522A with Cdk5/p35, GSK3b, or both. This result suggests that CSK3b as well as Cdk5 phosphorylated CRMP2 at Ser522, or Cdk5 phosphorylation of Ser522 is essential for the additional phosphorylation of CRMP2 by GSK3b. In vitro kinase assay using purified protein GSK3b alone did not phosphorylate CRMP2.
Uchida Y, Ohshima T, Sasaki Y, Suzuki H, Yanai S, Yamashita N, Nakamura F, Takei K, Ihara Y, Mikoshiba K, Kolattukudy P, Honnorat J, Goshima Y (2005) Semaphorin3A signalling is mediated via sequential Cdk5 and GSK3beta phosphorylation of CRMP2: implication of common phosphorylating mechanism underlying axon guidance and Alzheimer’s disease. Genes Cells 10:165–179. Wang LH, Strittmatter SM (1996) A family of rat CRMP genes is differentially expressed in the nervous system. J Neurosci 16:6197–6207.
Synapsin I bundles F-actin in a phosphorylationdependent manner. Nature 326, 704–707. P. (1997). Amphiphysin I is associated with coated endocytic intermediates and undergoes stimulation-dependent dephosphorylation in nerve terminals. J. Biol. Chem. 272, 30984–30992. , and Greengard, P. (1990). Timeresolved fluorescence study of the neuron-specific phosphoprotein synapsin I. Evidence for phosphorylation-dependent conformational changes. J. Biol. Chem. 265, 12584–12595. T. (2004). Co-purification and localization of Munc18-1 (p67) and Cdk5 with neuronal cytoskeletal proteins.