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relying on or requiring a person or thing for support, supply, or what is needed; "dependent children"; "dependent on moisture"
addicted to a drug (同)dependant, drug-addicted, hooked, strung-out
contingent on something else (同)dependant, qualified
(of a clause) unable to stand alone syntactically as a complete sentence; "a subordinate (or dependent) clause functions as a noun or adjective or adverb within a sentence" (同)subordinate
an enzyme that catalyzes the conversion of a proenzyme to an active enzyme
the basic unit of money in Papua New Guinea

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『頼っている』,依存している,従属している / 扶養される人(家族)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/08/24 15:00:30」(JST)

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Cell division protein kinase 5 is an enzyme that in humans is encoded by the CDK5 gene.^[1]^[1]^[2]^[2] The protein encoded by this gene is part of the cyclin-dependent kinase family.

Physiological Role

Recently Cdk5 has emerged as an essential kinase in sensory pathways. Recent reports of Pareek et al. from NIH suggest its necessity in pain signaling. CDK5 is required for proper development of the brain and to be activated, CDK5 must associate with CDK5R1 or CDK5R2.^[3]^[4] Unlike other cyclin dependent kinases, CDK5 does not also require phosphorylation on the T loop so that binding with the activator is sufficient to activate the kinase.^[5]

Cdk5 is involved in the processes of neuronal maturation^[6] and migration, phosphorylating the key intracellular adaptor of the reelin signaling chain.^[7]

Experiments performed on mice lacking p35, a necessary activator of cdk5 in early brain development, showed that the normal layering of neurons was reversed in the cortex. This disrupted lamination again implicated cdk5 in neuronal migration and plasticity.^[8]

Cdk5 is also involved in the regulation of synaptic vesicle exocytosis via phosphorylation of munc-18.^[9]

Role in Disease

Dysregulation of this enzyme has been implicated in several neurodegenerative diseases^[10] including Alzheimer's.^[11]^[12]

It is involved in invasive cancers, apparently by reducing the activity of the actin regulatory protein caldesmon.^[13]

History

CDK5 was originally named NCLK for Neuronal CDC2-Like Kinase due to its similar phosphorylation motif. CDK5 in combination with an activator was also referred to as Tau Protein Kinase II.^[14] Furthermore, Cdk5 has been reported to be involved in T cell activation and play an important role in development of autoimmune disorders, such as multiple sclerosis.^[15]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^[16]

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Nicotine Activity on Dopaminergic Neurons edit

Interactions

Cyclin-dependent kinase 5 has been shown to interact with LMTK2,^[17] NDEL1,^[18] CDK5R1,^[5]^[19] Nestin^[20] and PAK1.^[21]

References

^ ^a ^b Demetrick DJ, Zhang H, Beach DH (February 1994). "Chromosomal mapping of human CDK2, CDK4, and CDK5 cell cycle kinase genes". Cytogenet Cell Genet 66 (1): 72–4. doi:10.1159/000133669. PMID 8275715.
^ ^a ^b Meyerson M, Enders GH, Wu CL, Su LK, Gorka C, Nelson C, Harlow E, Tsai LH (August 1992). "A family of human cdc2-related protein kinases". EMBO J 11 (8): 2909–17. PMC 556772. PMID 1639063. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=556772.
^ Patrick GN, Zukerberg L, Nikolic M, de la Monte S, Dikkes P, Tsai LH (1999). "Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration". Nature 402 (6762): 615–22. doi:10.1038/45159. PMID 10604467.
^ Paglini G, Cáceres A (2001). "The role of the Cdk5--p35 kinase in neuronal development". Eur. J. Biochem. 268 (6): 1528–33. doi:10.1046/j.1432-1327.2001.02023.x. PMID 11248669.
^ ^a ^b Tarricone C, Dhavan R, Peng J, Areces LB, Tsai LH, Musacchio A (September 2001). "Structure and regulation of the CDK5-p25(nck5a) complex". Mol. Cell 8 (3): 657–69. doi:10.1016/S1097-2765(01)00343-4. PMID 11583627. http://linkinghub.elsevier.com/retrieve/pii/S1097-2765(01)00343-4.
^ Jessberger S, Aigner S, Clemenson GD, et al. (November 2008). Danzer, Steve. ed. "Cdk5 Regulates Accurate Maturation of Newborn Granule Cells in the Adult Hippocampus". PLoS Biol. 6 (11): e272. doi:10.1371/journal.pbio.0060272. PMC 2581629. PMID 18998770. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2581629.
^ Ohshima T, Suzuki H, Morimura T, Ogawa M, Mikoshiba K (April 2007). "Modulation of Reelin signaling by Cyclin-dependent kinase 5". Brain Res. 1140: 84–95. doi:10.1016/j.brainres.2006.01.121. PMID 16529723. http://linkinghub.elsevier.com/retrieve/pii/S0006-8993(06)00373-8.
^ Rakic S, Yanagawa Y, Obata K, Faux C, Parnavelas J, Nikolic M (November 2008). "Cortical Interneurons Require p35/Cdk5 for their Migration and Laminar Organization". Cerebral Cortex 19 (8): 1857–69. doi:10.1093/cercor/bhn213. PMC 2705696. PMID 19037081. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2705696.
^ Fletcher AI, Shuang R, Giovannucci DR, Zhang L, Bittner MA, Stuenkel EL (February 1999). "Regulation of exocytosis by cyclin-dependent kinase 5 via phosphorylation of Munc18". J Biol Chem 274 (7): 4027–35. doi:10.1074/jbc.274.7.4027. PMID 9933594.
^ Dhavan R, Tsai LH (2001). "A decade of CDK5". Nat. Rev. Mol. Cell Biol. 2 (10): 749–59. doi:10.1038/35096019. PMID 11584302.
^ Monaco EA (2004). "Recent evidence regarding a role for Cdk5 dysregulation in Alzheimer's disease". Curr Alzheimer Res 1 (1): 33–8. doi:10.2174/1567205043480519. PMID 15975083. http://www.ingentaconnect.com/content/ben/car/2004/00000001/00000001/art00005.
^ Qu J (2011). "S-Nitrosylation activates Cdk5 and contributes to synaptic spine loss induced by β-amyloid peptide". PNAS 108 (34): 14330–5. doi:10.1073/pnas.1105172108. PMID 21844361. http://www.pnas.org/content/108/34/14330.
^ Quintavalle, M.; Elia, L.; Price, J. H.; Heynen-Genel, S.; Courtneidge, S. A. (2011). "A Cell-Based High-Content Screening Assay Reveals Activators and Inhibitors of Cancer Cell Invasion". Science Signaling 4 (183): ra49. doi:10.1126/scisignal.2002032. PMID 21791703. http://stke.sciencemag.org/cgi/content/abstract/sigtrans;4/183/ra49.
^ Kobayashi S, Ishiguro K, Omori A, Takamatsu M, Arioka M, Imahori K, Uchida T. (1993). "A cdc2-related kinase PSSALRE/cdk5 is homologous with the 30 kDa subunit of tau protein kinase II, a proline-directed protein kinase associated with microtubule". FEBS Letters 335 (2): 171–175. doi:10.1016/0014-5793(93)80723-8. PMID 8253190.
^ Pareek TK, Lam E, Zheng X, Askew D, Kulkarni AB, Chance MR, Huang AY, Cooke KR, Letterio JJ (October 2010). "Cyclin-dependent kinase 5 activity is required for T cell activation and induction of experimental autoimmune encephalomyelitis". J. Exp. Med. 207 (11): 2507–19. doi:10.1084/jem.20100876. PMC 2964575. PMID 20937706. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2964575.
^ The interactive pathway map can be edited at WikiPathways: "NicotineDopaminergic_WP1602". http://www.wikipathways.org/index.php/Pathway:WP1602.
^ Kesavapany, Sashi; Lau Kwok-Fai, Ackerley Steven, Banner Steven J, Shemilt Stephen J A, Cooper Jonathan D, Leigh P Nigel, Shaw Christopher E, McLoughlin Declan M, Miller Christopher C J (June 2003). "Identification of a novel, membrane-associated neuronal kinase, cyclin-dependent kinase 5/p35-regulated kinase". J. Neurosci. (United States) 23 (12): 4975–83. PMID 12832520.
^ Niethammer, M; Smith D S, Ayala R, Peng J, Ko J, Lee M S, Morabito M, Tsai L H (December 2000). "NUDEL is a novel Cdk5 substrate that associates with LIS1 and cytoplasmic dynein". Neuron (United States) 28 (3): 697–711. doi:10.1016/S0896-6273(00)00147-1. ISSN 0896-6273. PMID 11163260.
^ Chen, F; Studzinski G P (June 2001). "Expression of the neuronal cyclin-dependent kinase 5 activator p35Nck5a in human monocytic cells is associated with differentiation". Blood (United States) 97 (12): 3763–7. doi:10.1182/blood.V97.12.3763. ISSN 0006-4971. PMID 11389014.
^ Sahlgren, Cecilia M; Mikhailov Andrey, Vaittinen Samuli, Pallari Hanna-Mari, Kalimo Hannu, Pant Harish C, Eriksson John E (July 2003). "Cdk5 Regulates the Organization of Nestin and Its Association with p35". Mol. Cell. Biol. (United States) 23 (14): 5090–106. doi:10.1128/MCB.23.14.5090-5106.2003. ISSN 0270-7306. PMC 162223. PMID 12832492. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=162223.
^ Rashid, T; Banerjee M, Nikolic M (December 2001). "Phosphorylation of Pak1 by the p35/Cdk5 kinase affects neuronal morphology". J. Biol. Chem. (United States) 276 (52): 49043–52. doi:10.1074/jbc.M105599200. ISSN 0021-9258. PMID 11604394.

External links

Cyclin-Dependent+Kinase+5 at the US National Library of Medicine Medical Subject Headings (MeSH)

This article on a gene on chromosome 7 is a stub. You can help Wikipedia by expanding it.

UpToDate Contents

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English Journal

Cdk5 is a New Rapid Synaptic Homeostasis Regulator Capable of Initiating the Early Alzheimer-Like Pathology.

Sheng Y1, Zhang L2, Su SC3, Tsai LH3, Julius Zhu J2.
Cerebral cortex (New York, N.Y. : 1991).Cereb Cortex.2016 Jul;26(7):2937-51. doi: 10.1093/cercor/bhv032. Epub 2015 Jun 17.
Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase implicated in synaptic plasticity, behavior, and cognition, yet its synaptic function remains poorly understood. Here, we report that physiological Cdk5 signaling in rat hippocampal CA1 neurons regulates homeostatic synaptic transmission
PMID 26088971

Pharmacological modulation of protein kinases as a new approach to treat addiction to cocaine and opiates.

García-Pardo MP1, Roger-Sanchez C1, Rodríguez-Arias M1, Miñarro J1, Aguilar MA2.
European journal of pharmacology.Eur J Pharmacol.2016 Jun 15;781:10-24. doi: 10.1016/j.ejphar.2016.03.065. Epub 2016 Apr 4.
Drug addiction shares brain mechanisms and molecular substrates with learning and memory processes, such as the stimulation of glutamate receptors and their downstream signalling pathways. In the present work we provide an up-to-date review of studies that have demonstrated the implication of the ma
PMID 27056740

p120-catenin is necessary for neuroprotection induced by CDK5 silencing in models of Alzheimer's disease.

Uribe-Arias A1, Posada-Duque RA1, González-Billault C2,3, Villegas A1, Lopera F1, Cardona-Gómez GP1.
Journal of neurochemistry.J Neurochem.2016 Jun 8. doi: 10.1111/jnc.13697. [Epub ahead of print]
Cyclin-dependent kinase 5 (CDK5) plays important roles in synaptic function. Its unregulated over-activation has been, however, associated with neurodegeneration in Alzheimer's disease. Our previous studies revealed that CDK5 silencing ameliorates tauopathy and spatial memory impairment in the 3xTgA
PMID 27273428

Japanese Journal

Short-term Cultivation of Porcine Cumulus Cells Influences the Cyclin-dependent Kinase 4 (Cdk4) and Connexin 43 (Cx43) Protein Expression : A Real-time Cell Proliferation Approach

KEMPISTY Bartosz,ZIOLKOWSKA Agnieszka,PIOTROWSKA Hanna [他]
The journal of reproduction and development 59(4), 339-345, 2013-08
NAID 40019763775

Heterogeneous Nuclear Ribonucleoprotein R Cooperates with Mediator to Facilitate Transcription Reinitiation on the c-Fos Gene

Fukuda Aya,Shimada Miho,Nakadai Tomoyoshi,Nishimura Ken,Hisatake Koji,福田綾,西村健,久武幸司
PLoS ONE 8(8), e72496, 2013-08
… The cooperative action of hnRNP R and Mediator is diminished by the cyclin-dependent kinase 8 (CDK8) module, which is comprised of CDK8, Cyclin C, MED12 and MED13 of the Mediator subunits. …
NAID 120005324989

Simultaneous Inactivation of the p16, p15 and p14 Genes Encoding Cyclin-Dependent Kinase Inhibitors in Canine T-Lymphoid Tumor Cells

FUJIWARA-IGARASHI Aki,GOTO-KOSHINO Yuko,MOCHIZUKI Hiroyuki [他]
The journal of veterinary medical science 75(6), 733-742, 2013-06
NAID 40019727246

「サイクリン依存性キナーゼ5」

Cyclin-dependent kinase 5
	; PDB rendering based on 1h41.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1H4L, 1UNG, 1UNH, 1UNL, 3O0G
Identifiers
Symbols	CDK5; PSSALRE
External IDs	OMIM: 123831 MGI: 101765 HomoloGene: 3623 ChEMBL: 4036 GeneCards: CDK5 Gene
EC number	2.7.11.22
Gene Ontology
Molecular function	• p53 binding; • protein kinase activity; • protein serine/threonine kinase activity; • protein serine/threonine kinase activity; • protein serine/threonine kinase activity; • cyclin-dependent protein kinase activity; • ErbB-2 class receptor binding; • protein binding; • ATP binding; • kinase activity; • acetylcholine receptor activator activity; • ErbB-3 class receptor binding; • tau-protein kinase activity;
Cellular component	• nucleus; • cytoplasm; • cytosol; • plasma membrane; • postsynaptic density; • membrane; • cyclin-dependent protein kinase 5 holoenzyme complex; • lamellipodium; • cell junction; • filopodium; • axon; • dendrite; • growth cone; • neuromuscular junction; • neuronal cell body; • perikaryon; • postsynaptic membrane;
Biological process	• neuron migration; • synaptic transmission, dopaminergic; • protein phosphorylation; • intracellular protein transport; • nucleocytoplasmic transport; • cell cycle; • cell cycle; • cell-matrix adhesion; • synaptic transmission; • axon guidance; • synapse assembly; • skeletal muscle tissue development; • blood coagulation; • motor axon guidance; • cell proliferation; • visual learning; • activation of pro-apoptotic gene products; • embryo development; • Schwann cell development; • synaptic vesicle exocytosis; • phosphorylation; • phosphorylation; • peptidyl-serine phosphorylation; • sensory perception of pain; • cerebellar cortex formation; • hippocampus development; • layer formation in cerebral cortex; • central nervous system neuron development; • corpus callosum development; • neuron differentiation; • neuron differentiation; • regulation of cell migration; • cortical actin cytoskeleton organization; • neuron projection development; • negative regulation of protein ubiquitination; • negative regulation of synaptic plasticity; • receptor catabolic process; • serine phosphorylation of STAT3 protein; • synaptic transmission, glutamatergic; • regulation of apoptotic process; • receptor clustering; • positive regulation of neuron apoptotic process; • regulated secretory pathway; • negative regulation of cell cycle; • positive regulation of protein kinase activity; • negative regulation of transcription, DNA-dependent; • positive regulation of calcium ion-dependent exocytosis; • protein autophosphorylation; • negative regulation of protein export from nucleus; • behavioral response to cocaine; • regulation of synaptic plasticity; • regulation of synaptic plasticity; • synaptic vesicle endocytosis; • axon extension; • oligodendrocyte differentiation; • dendrite morphogenesis; • cell division; • neuron apoptotic process; • regulation of excitatory postsynaptic membrane potential; • regulation of dendritic spine morphogenesis; • regulation of cell cycle arrest; • positive regulation of actin cytoskeleton reorganization;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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