Cdk5

Summary

Gene Symbol: Cdk5
Description: cyclin-dependent kinase 5
Alias: AW048668, Crk6, cyclin-dependent-like kinase 5, CR6 protein kinase, TPKII catalytic subunit, cell division protein kinase 5, serine/threonine-protein kinase PSSALRE, tau protein kinase II catalytic subunit
Species: mouse
Products:     Cdk5

Top Publications

  1. Hirota Y, Ohshima T, Kaneko N, Ikeda M, Iwasato T, Kulkarni A, et al. Cyclin-dependent kinase 5 is required for control of neuroblast migration in the postnatal subventricular zone. J Neurosci. 2007;27:12829-38 pubmed
    ..Here, we report a novel role for cyclin-dependent kinase 5 (Cdk5), a neuronal protein kinase, in this process...
  2. Sun K, de Pablo Y, Vincent F, Shah K. Deregulated Cdk5 promotes oxidative stress and mitochondrial dysfunction. J Neurochem. 2008;107:265-78 pubmed publisher
    ..A chemical genetic screen revealed that deregulated cyclin-dependent kinase 5 (Cdk5) may cause oxidative stress by compromising the cellular anti-oxidant defense system...
  3. Zhang J, Li H, Herrup K. Cdk5 nuclear localization is p27-dependent in nerve cells: implications for cell cycle suppression and caspase-3 activation. J Biol Chem. 2010;285:14052-61 pubmed publisher
    ..We have previously shown that the cyclin-dependent kinase Cdk5 is an important part of this process, but only when it is present in the nucleus...
  4. Kawauchi T, Chihama K, Nabeshima Y, Hoshino M. Cdk5 phosphorylates and stabilizes p27kip1 contributing to actin organization and cortical neuronal migration. Nat Cell Biol. 2006;8:17-26 pubmed
    ..Here, we show that Cdk5, an unconventional neuronal CDK, phosphorylates and stabilizes p27 as an upstream regulator, maintaining the amount ..
  5. Hawasli A, Benavides D, Nguyen C, Kansy J, Hayashi K, Chambon P, et al. Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control of NMDAR degradation. Nat Neurosci. 2007;10:880-886 pubmed publisher
    ..Although the neuronal protein kinase cyclin-dependent kinase 5 (Cdk5) has been implicated in cognitive disorders, its role in learning has been obscured by the perinatal lethality of ..
  6. Morabito M, Sheng M, Tsai L. Cyclin-dependent kinase 5 phosphorylates the N-terminal domain of the postsynaptic density protein PSD-95 in neurons. J Neurosci. 2004;24:865-76 pubmed
    ..The N-terminal domain of PSD-95 contains three consensus phosphorylation sites for cyclin-dependent kinase 5 (cdk5), a proline-directed serine-threonine kinase essential for brain development and implicated in synaptic plasticity, ..
  7. Paoletti P, Vila I, Rife M, Lizcano J, Alberch J, Gines S. Dopaminergic and glutamatergic signaling crosstalk in Huntington's disease neurodegeneration: the role of p25/cyclin-dependent kinase 5. J Neurosci. 2008;28:10090-101 pubmed publisher
    ..underlying mechanism of increased striatal vulnerability, we identified aberrant cyclin-dependent kinase 5 (Cdk5) activation...
  8. Cheung Z, Chin W, Chen Y, Ng Y, Ip N. Cdk5 is involved in BDNF-stimulated dendritic growth in hippocampal neurons. PLoS Biol. 2007;5:e63 pubmed
    ..Recent studies reveal that cyclin-dependent kinase 5 (Cdk5), a serine/threonine kinase, may modulate RTK signaling through phosphorylation of the receptor...
  9. Smith P, Mount M, Shree R, Callaghan S, Slack R, Anisman H, et al. Calpain-regulated p35/cdk5 plays a central role in dopaminergic neuron death through modulation of the transcription factor myocyte enhancer factor 2. J Neurosci. 2006;26:440-7 pubmed
    ..Here, we provide evidence that the downstream effector pathway of calpains is through cyclin-dependent kinase 5 (cdk5)-mediated modulation of the transcription factor myocyte enhancer factor 2 (MEF2)...

More Information

Publications82

  1. Fu A, Fu W, Ng A, Chien W, Ng Y, Wang J, et al. Cyclin-dependent kinase 5 phosphorylates signal transducer and activator of transcription 3 and regulates its transcriptional activity. Proc Natl Acad Sci U S A. 2004;101:6728-33 pubmed
    The activity of cyclin-dependent kinase 5 (Cdk5) depends on the association with one of its activators, p35 and p39, which are prominently expressed in the nervous system...
  2. Smith P, Crocker S, Jackson Lewis V, Jordan Sciutto K, Hayley S, Mount M, et al. Cyclin-dependent kinase 5 is a mediator of dopaminergic neuron loss in a mouse model of Parkinson's disease. Proc Natl Acad Sci U S A. 2003;100:13650-5 pubmed
    ..Here, we report that cdk5 expression and activity are elevated after administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a ..
  3. Yamashita N, Morita A, Uchida Y, Nakamura F, Usui H, Ohshima T, et al. Regulation of spine development by semaphorin3A through cyclin-dependent kinase 5 phosphorylation of collapsin response mediator protein 1. J Neurosci. 2007;27:12546-54 pubmed
    ..This attenuation was also seen in cyclin-dependent kinase 5 (cdk5)-/- neurons...
  4. Ohshima T, Gilmore E, Longenecker G, Jacobowitz D, Brady R, Herrup K, et al. Migration defects of cdk5(-/-) neurons in the developing cerebellum is cell autonomous. J Neurosci. 1999;19:6017-26 pubmed
    Cyclin-dependent kinase 5 (Cdk5) is a member of the family of cell cycle-related kinases. Previous neuropathological analysis of cdk5(-/-) mice showed significant changes in CNS development in regions from cerebral cortex to brainstem...
  5. Benavides D, Quinn J, Zhong P, Hawasli A, DiLeone R, Kansy J, et al. Cdk5 modulates cocaine reward, motivation, and striatal neuron excitability. J Neurosci. 2007;27:12967-76 pubmed
    Cyclin-dependent kinase 5 (Cdk5) regulates dopamine neurotransmission and has been suggested to serve as a homeostatic target of chronic psychostimulant exposure...
  6. Asada A, Saito T, Hisanaga S. Phosphorylation of p35 and p39 by Cdk5 determines the subcellular location of the holokinase in a phosphorylation-site-specific manner. J Cell Sci. 2012;125:3421-9 pubmed publisher
    b>Cdk5 is a member of the cyclin-dependent kinase (Cdk) family, which is activated by neuronal activators p35 or p39. Cdk5 regulates a variety of neuronal activities including migration, synaptic activity and neuronal death...
  7. Li B, Zhang L, Takahashi S, Ma W, Jaffe H, Kulkarni A, et al. Cyclin-dependent kinase 5 prevents neuronal apoptosis by negative regulation of c-Jun N-terminal kinase 3. EMBO J. 2002;21:324-33 pubmed
    Cyclin-dependent kinase 5 (cdk5) is a serine/threonine kinase activated by associating with its neuron-specific activators p35 and p39...
  8. Utreras E, Keller J, Terse A, Prochazkova M, Iadarola M, Kulkarni A. Transforming growth factor-?1 regulates Cdk5 activity in primary sensory neurons. J Biol Chem. 2012;287:16917-29 pubmed publisher
    In addition to many important roles for Cdk5 in brain development and synaptic function, we reported previously that Cdk5 regulates inflammatory pain signaling, partly through phosphorylation of transient receptor potential vanilloid 1 (..
  9. Fu W, Chen Y, Sahin M, Zhao X, Shi L, Bikoff J, et al. Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanism. Nat Neurosci. 2007;10:67-76 pubmed
    ..Here we report an important function of cyclin-dependent kinase 5 (Cdk5) in EphA4-dependent spine retraction in mice...
  10. Horiuchi Y, Asada A, Hisanaga S, Toh e A, Nishizawa M. Identifying novel substrates for mouse Cdk5 kinase using the yeast Saccharomyces cerevisiae. Genes Cells. 2006;11:1393-404 pubmed
    Among the mammalian Cdk family members, Cdk5, activated by the binding of p35, plays an important role in the control of neurogenesis, and its deregulation is thought to be one of the causes of neurodegenerative diseases...
  11. Takahashi S, Ohshima T, Hirasawa M, Pareek T, Bugge T, Morozov A, et al. Conditional deletion of neuronal cyclin-dependent kinase 5 in developing forebrain results in microglial activation and neurodegeneration. Am J Pathol. 2010;176:320-9 pubmed publisher
    ..An essential role of cyclin-dependent kinase 5 (Cdk5) in brain development has been demonstrated in Cdk5(-/-) mice, which show neuronal migration defects and perinatal ..
  12. Ahuja H, Zhu Y, Zakeri Z. Association of cyclin-dependent kinase 5 and its activator p35 with apoptotic cell death. Dev Genet. 1997;21:258-67 pubmed
    ..the role of cyclin-dependent kinases in cell death and found that the expression of cyclin-dependent kinase 5 (Cdk5) is associated with apoptotic cell death in both adult and embryonic tissues...
  13. O Hare M, Kushwaha N, Zhang Y, Aleyasin H, Callaghan S, Slack R, et al. Differential roles of nuclear and cytoplasmic cyclin-dependent kinase 5 in apoptotic and excitotoxic neuronal death. J Neurosci. 2005;25:8954-66 pubmed
    Cyclin-dependent kinase 5 (cdk5) is a member of the cyclin-dependent kinase family whose activity is localized mainly to postmitotic neurons attributable to the selective expression of its activating partners p35 and p39...
  14. Rosales J, Ernst J, Hallows J, Lee K. GTP-dependent secretion from neutrophils is regulated by Cdk5. J Biol Chem. 2004;279:53932-6 pubmed
    ..Cyclin-dependent kinase 5 (Cdk5), the various substrates of which include Munc18 and synapsin 1, has been implicated in neuronal secretion...
  15. Kaminosono S, Saito T, Oyama F, Ohshima T, Asada A, Nagai Y, et al. Suppression of mutant Huntingtin aggregate formation by Cdk5/p35 through the effect on microtubule stability. J Neurosci. 2008;28:8747-55 pubmed publisher
    ..We show Cdk5/p35 suppresses the formation of mhtt inclusion bodies in cell lines and primary neurons...
  16. Zhang J, Cicero S, Wang L, Romito Digiacomo R, Yang Y, Herrup K. Nuclear localization of Cdk5 is a key determinant in the postmitotic state of neurons. Proc Natl Acad Sci U S A. 2008;105:8772-7 pubmed publisher
    Cyclin-dependent kinase 5 (Cdk5) is a nontraditional Cdk that is primarily active in postmitotic neurons. Its best known substrates are cytoskeletal proteins. Less appreciated is its role in the maintenance of a postmitotic state...
  17. Hawasli A, Koovakkattu D, Hayashi K, Anderson A, Powell C, Sinton C, et al. Regulation of hippocampal and behavioral excitability by cyclin-dependent kinase 5. PLoS ONE. 2009;4:e5808 pubmed publisher
    Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase that has been implicated in learning, synaptic plasticity, neurotransmission, and numerous neurological disorders...
  18. Rakic S, Davis C, Molnar Z, Nikolic M, Parnavelas J. Role of p35/Cdk5 in preplate splitting in the developing cerebral cortex. Cereb Cortex. 2006;16 Suppl 1:i35-45 pubmed
    ..To investigate the role of the cyclin-dependent kinase 5 (Cdk5) and its activator p35 in preplate splitting, we used Nissl staining, carbocyanine dye tracing, cell birthdating, ..
  19. Cicero S, Herrup K. Cyclin-dependent kinase 5 is essential for neuronal cell cycle arrest and differentiation. J Neurosci. 2005;25:9658-68 pubmed
    Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase with significant homology to cell cycle-related Cdks but is not believed to be active in a typical cell cycle...
  20. Tanaka T, Veeranna -, Ohshima T, Rajan P, Amin N, Cho A, et al. Neuronal cyclin-dependent kinase 5 activity is critical for survival. J Neurosci. 2001;21:550-8 pubmed
    Cyclin-dependent kinase 5 (Cdk5) null mice exhibit a unique phenotype characterized by perinatal mortality, disrupted cerebral cortical layering attributable to abnormal neuronal migration, lack of cerebellar foliation, and chromatolytic ..
  21. Ohshima T, Hirasawa M, Tabata H, Mutoh T, Adachi T, Suzuki H, et al. Cdk5 is required for multipolar-to-bipolar transition during radial neuronal migration and proper dendrite development of pyramidal neurons in the cerebral cortex. Development. 2007;134:2273-82 pubmed
    ..Mice lacking Cdk5 exhibit abnormal corticogenesis owing to neuronal migration defects...
  22. Lazaro J, Kitzmann M, Poul M, Vandromme M, Lamb N, Fernandez A. Cyclin dependent kinase 5, cdk5, is a positive regulator of myogenesis in mouse C2 cells. J Cell Sci. 1997;110 ( Pt 10):1251-60 pubmed
    We have examined the expression, activity and localization of cyclin dependent kinase 5 (cdk5), during myogenesis. Cdk5 protein was found expressed in adult mouse muscle...
  23. Remedios R, Huilgol D, Saha B, Hari P, Bhatnagar L, Kowalczyk T, et al. A stream of cells migrating from the caudal telencephalon reveals a link between the amygdala and neocortex. Nat Neurosci. 2007;10:1141-50 pubmed
    ..share mechanisms for specification (transcription factors Tbr1, Lhx2 and Emx1/2) and migration (reelin and Cdk5)...
  24. He Y, Li H, Xie W, Yang C, Yu A, Wang Y. The presence of active Cdk5 associated with p35 in astrocytes and its important role in process elongation of scratched astrocyte. Glia. 2007;55:573-83 pubmed
    Cyclin-dependent kinase 5 (Cdk5) is a unique member of the Cdk family; its kinase activity requires association with its activator, p35 or p39. p35 is the strongest and best characterized activator...
  25. Sun K, Lee H, Smith M, Shah K. Direct and indirect roles of cyclin-dependent kinase 5 as an upstream regulator in the c-Jun NH2-terminal kinase cascade: relevance to neurotoxic insults in Alzheimer's disease. Mol Biol Cell. 2009;20:4611-9 pubmed publisher
    Significant increase in JNK, c-Jun, and Cdk5 activities are reported in Alzheimer's disease (AD). Inhibition of c-Jun prevents neuronal cell death in in vivo AD models, highlighting it as a major JNK effector...
  26. Fu A, Ip F, Fu W, Cheung J, Wang J, Yung W, et al. Aberrant motor axon projection, acetylcholine receptor clustering, and neurotransmission in cyclin-dependent kinase 5 null mice. Proc Natl Acad Sci U S A. 2005;102:15224-9 pubmed
    Cyclin-dependent kinase (Cdk)5 is a key regulator of neural development. We have previously demonstrated that Cdk5/p35 are localized to the postsynaptic muscle and are implicated in the regulation of neuregulin/ErbB signaling in myotube ..
  27. He X, Takahashi S, Suzuki H, Hashikawa T, Kulkarni A, Mikoshiba K, et al. Hypomyelination phenotype caused by impaired differentiation of oligodendrocytes in Emx1-cre mediated Cdk5 conditional knockout mice. Neurochem Res. 2011;36:1293-303 pubmed publisher
    Cyclin-dependent kinase 5 (Cdk5) plays a pivotal role in neuronal migration and differentiation, and in axonal elongation...
  28. Miyamoto Y, Yamauchi J, Chan J, Okada A, Tomooka Y, Hisanaga S, et al. Cdk5 regulates differentiation of oligodendrocyte precursor cells through the direct phosphorylation of paxillin. J Cell Sci. 2007;120:4355-66 pubmed
    ..we show that cyclin-dependent kinase (Cdk) 5 is activated following the induction of differentiation, and that the Cdk5 inhibitor roscovitine inhibits OL differentiation...
  29. Xie Z, Sanada K, Samuels B, Shih H, Tsai L. Serine 732 phosphorylation of FAK by Cdk5 is important for microtubule organization, nuclear movement, and neuronal migration. Cell. 2003;114:469-82 pubmed
    The serine/threonine kinase Cdk5 plays an essential role in neuronal positioning during corticogenesis, but the underlying mechanisms are unknown...
  30. Meyer D, Richer E, Benkovic S, Hayashi K, Kansy J, Hale C, et al. Striatal dysregulation of Cdk5 alters locomotor responses to cocaine, motor learning, and dendritic morphology. Proc Natl Acad Sci U S A. 2008;105:18561-6 pubmed publisher
    ..Cyclin-dependent kinase 5 (Cdk5) regulates striatal dopamine neurotransmission and behavioral responses to cocaine...
  31. Zhang J, Li H, Yabut O, Fitzpatrick H, D ARCANGELO G, Herrup K. Cdk5 suppresses the neuronal cell cycle by disrupting the E2F1-DP1 complex. J Neurosci. 2010;30:5219-28 pubmed publisher
    ..Our laboratory has shown that cyclin-dependent kinase 5 (Cdk5) is a potent cell cycle suppressor, and we report here on the molecular basis of this activity...
  32. Zhang Q, Ahuja H, Zakeri Z, Wolgemuth D. Cyclin-dependent kinase 5 is associated with apoptotic cell death during development and tissue remodeling. Dev Biol. 1997;183:222-33 pubmed
    ..of the cyclin-dependent kinase (Cdk) family members in reproductive organs, we observed a striking expression of Cdk5 in atretic follicles in the ovary, particularly in granulosa cells that appeared to be dying...
  33. Li Z, David G, Hung K, Depinho R, Fu A, Ip N. Cdk5/p35 phosphorylates mSds3 and regulates mSds3-mediated repression of transcription. J Biol Chem. 2004;279:54438-44 pubmed
    Cyclin-dependent kinase 5 (Cdk5), a serine/threonine kinase that displays kinase activity predominantly in neurons, is activated by two non-cyclin activators, p35 or p39...
  34. Lilja L, Johansson J, Gromada J, Mandic S, Fried G, Berggren P, et al. Cyclin-dependent kinase 5 associated with p39 promotes Munc18-1 phosphorylation and Ca(2+)-dependent exocytosis. J Biol Chem. 2004;279:29534-41 pubmed
    Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine protein kinase that requires association with a regulatory protein, p35 or p39, to form an active enzyme...
  35. Jessberger S, Aigner S, Clemenson G, Toni N, Lie D, Karalay O, et al. Cdk5 regulates accurate maturation of newborn granule cells in the adult hippocampus. PLoS Biol. 2008;6:e272 pubmed publisher
    ..Here we show that single-cell-specific knockdown of cyclin-dependent kinase 5 (cdk5) activity in newborn cells using a retrovirus-based strategy leads to aberrant growth of dendritic processes, which ..
  36. Tsai L, Takahashi T, Caviness V, Harlow E. Activity and expression pattern of cyclin-dependent kinase 5 in the embryonic mouse nervous system. Development. 1993;119:1029-40 pubmed
    Cyclin-dependent kinase 5 (cdk5) was originally isolated on the basis of its close primary sequence homology to the human cdc2 serine/threonine kinase, the prototype of the cyclin-dependent kinases...
  37. Ohshima T, Suzuki H, Morimura T, Ogawa M, Mikoshiba K. Modulation of Reelin signaling by Cyclin-dependent kinase 5. Brain Res. 2007;1140:84-95 pubmed
    The Reelin signaling and Cyclin-dependent kinase 5 (Cdk5) both regulate neuronal positioning in the developing brain...
  38. Samuels B, Hsueh Y, Shu T, Liang H, Tseng H, Hong C, et al. Cdk5 promotes synaptogenesis by regulating the subcellular distribution of the MAGUK family member CASK. Neuron. 2007;56:823-37 pubmed
    ..Furthermore, Cdk5 gain of function results in an increased number of synapses in vivo...
  39. Niethammer M, Smith D, Ayala R, Peng J, Ko J, Lee M, et al. NUDEL is a novel Cdk5 substrate that associates with LIS1 and cytoplasmic dynein. Neuron. 2000;28:697-711 pubmed
    ..Furthermore, NUDEL is a substrate of Cdk5, a kinase known to be critical during neuronal migration...
  40. Cruz J, Tseng H, Goldman J, Shih H, Tsai L. Aberrant Cdk5 activation by p25 triggers pathological events leading to neurodegeneration and neurofibrillary tangles. Neuron. 2003;40:471-83 pubmed
    Cyclin-dependent kinase 5 (Cdk5) and its regulatory subunit p35 are integral players in the proper development of the mammalian central nervous system. Proteolytic cleavage of p35 generates p25, leading to aberrant Cdk5 activation...
  41. Wen Y, Yu W, Maloney B, Bailey J, Ma J, Marie I, et al. Transcriptional regulation of beta-secretase by p25/cdk5 leads to enhanced amyloidogenic processing. Neuron. 2008;57:680-90 pubmed publisher
    Cyclin-dependent kinase 5 (cdk5) has been implicated in Alzheimer's disease (AD) pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo...
  42. Lee J, Kim H, Lee S, Kim K. Stabilization and activation of p53 induced by Cdk5 contributes to neuronal cell death. J Cell Sci. 2007;120:2259-71 pubmed
    ..Cyclin-dependent kinase 5 (Cdk5), a proline-directed serine/threonine kinase, is most active in the central nervous system and plays a variety of ..
  43. Chang K, Vincent F, Shah K. Deregulated Cdk5 triggers aberrant activation of cell cycle kinases and phosphatases inducing neuronal death. J Cell Sci. 2012;125:5124-37 pubmed publisher
    ..The goal of this study was to investigate the mechanistic link between Cdk5 deregulation and cell cycle re-activation in ?-amyloid(1-42) (A?(1-42))-induced neurotoxicity...
  44. Tsai L, Delalle I, Caviness V, Chae T, Harlow E. p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5. Nature. 1994;371:419-23 pubmed
    Cyclin-dependent kinase 5 (Cdk5) was originally isolated through its structural homology to human Cdc2, a key regulator of cell-cycle progression...
  45. Tsutsumi K, Takano T, Endo R, Fukuda M, Ohshima T, Tomomura M, et al. Phosphorylation of AATYK1 by Cdk5 suppresses its tyrosine phosphorylation. PLoS ONE. 2010;5:e10260 pubmed publisher
    ..In this study, we investigated the interaction of AATYK1A with Cyclin-dependent kinase 5 (Cdk5)/p35, a proline-directed protein kinase that is predominantly expressed in neurons...
  46. Fischer A, Sananbenesi F, Schrick C, Spiess J, Radulovic J. Cyclin-dependent kinase 5 is required for associative learning. J Neurosci. 2002;22:3700-7 pubmed
    ..Here we identify, by subtractive hybridization, differential expression of the Cdk5 gene in response to stress...
  47. Hirasawa M, Ohshima T, Takahashi S, Longenecker G, Honjo Y, Veeranna -, et al. Perinatal abrogation of Cdk5 expression in brain results in neuronal migration defects. Proc Natl Acad Sci U S A. 2004;101:6249-54 pubmed
    Cyclin-dependent kinase 5 (Cdk5) is essential for the proper development of the CNS, as is evident from the perinatal lethality of conventional Cdk5 knockout (Cdk5-/-) mice...
  48. Sasaki Y, Cheng C, Uchida Y, Nakajima O, Ohshima T, Yagi T, et al. Fyn and Cdk5 mediate semaphorin-3A signaling, which is involved in regulation of dendrite orientation in cerebral cortex. Neuron. 2002;35:907-20 pubmed
    ..We observed that in fyn- and cdk5-deficient mice, Sema3A-induced growth cone collapse responses were attenuated compared to their heterologous ..
  49. de Thonel A, Ferraris S, Pallari H, Imanishi S, Kochin V, Hosokawa T, et al. Protein kinase Czeta regulates Cdk5/p25 signaling during myogenesis. Mol Biol Cell. 2010;21:1423-34 pubmed publisher
    ..PKCzeta was found to be associated with and to regulate the Cdk5/p35 signaling complex, an essential factor for both neuronal and myogenic differentiation...
  50. Tanaka T, Serneo F, Tseng H, Kulkarni A, Tsai L, Gleeson J. Cdk5 phosphorylation of doublecortin ser297 regulates its effect on neuronal migration. Neuron. 2004;41:215-27 pubmed
    Mutations in the doublecortin (DCX) gene in human or targeted disruption of the cdk5 gene in mouse lead to similar cortical lamination defects in the developing brain. Here we show that Dcx is phosphorylated by Cdk5...
  51. Lopes J, Oliveira C, Agostinho P. Neurodegeneration in an Abeta-induced model of Alzheimer's disease: the role of Cdk5. Aging Cell. 2010;9:64-77 pubmed publisher
    b>Cdk5 dysregulation is a major event in the neurodegenerative process of Alzheimer's disease (AD)...
  52. Ino H, Chiba T. Intracellular localization of cyclin-dependent kinase 5 (CDK5) in mouse neuron: CDK5 is located in both nucleus and cytoplasm. Brain Res. 1996;732:179-85 pubmed
    Cyclin-dependent kinase 5 (CDK5) is one of the cyclin-dependent kinases, and is expressed in mature neurons...
  53. Zhang J, Herrup K. Nucleocytoplasmic Cdk5 is involved in neuronal cell cycle and death in post-mitotic neurons. Cell Cycle. 2011;10:1208-14 pubmed
    ..One possible link is the atypical cyclin dependent kinase, Cdk5. Cdk5 exerts a double protective function in neurons, first by suppressing the cell cycle in the nucleus and second ..
  54. Liebl J, Fürst R, Vollmar A, Zahler S. Twice switched at birth: cell cycle-independent roles of the "neuron-specific" cyclin-dependent kinase 5 (Cdk5) in non-neuronal cells. Cell Signal. 2011;23:1698-707 pubmed publisher
    b>Cdk5 (cyclin-dependent kinase 5 or initially NCLK for neuronal CDC2-like kinase) was switched twice at its birth nearly twenty years ago: first it was thought to be cyclin-dependent, second it was assumed to be primarily of importance in ..
  55. Ko J, Humbert S, Bronson R, Takahashi S, Kulkarni A, Li E, et al. p35 and p39 are essential for cyclin-dependent kinase 5 function during neurodevelopment. J Neurosci. 2001;21:6758-71 pubmed
    Cyclin-dependent kinase 5 (Cdk5) plays a pivotal role in brain development and neuronal migration. Cdk5 is abundant in postmitotic, terminally differentiated neurons...
  56. Kwon Y, Tsai L. A novel disruption of cortical development in p35(-/-) mice distinct from reeler. J Comp Neurol. 1998;395:510-22 pubmed
    The p35/cdk5 neuronal-specific kinase complex has been shown to play an important role in the laminar configuration of cortical neurons. Mice lacking either p35 or cdk5 exhibit a disrupted cortical lamination pattern...
  57. Su S, Seo J, Pan J, Samuels B, Rudenko A, Ericsson M, et al. Regulation of N-type voltage-gated calcium channels and presynaptic function by cyclin-dependent kinase 5. Neuron. 2012;75:675-87 pubmed publisher
    ..Here we report that the N-type calcium channel is a substrate for cyclin-dependent kinase 5 (Cdk5)...
  58. Wei F, Nagashima K, Ohshima T, Saheki Y, Lu Y, Matsushita M, et al. Cdk5-dependent regulation of glucose-stimulated insulin secretion. Nat Med. 2005;11:1104-8 pubmed
    ..Here we show that inhibition of the activity of cyclin-dependent kinase 5 (Cdk5) enhanced insulin secretion under conditions of stimulation by high glucose but not low glucose in MIN6 cells and ..
  59. Li B, Ma W, Jaffe H, Zheng Y, Takahashi S, Zhang L, et al. Cyclin-dependent kinase-5 is involved in neuregulin-dependent activation of phosphatidylinositol 3-kinase and Akt activity mediating neuronal survival. J Biol Chem. 2003;278:35702-9 pubmed
    ..In this study, we reported that cyclin-dependent kinase-5 (Cdk5) regulates Akt activity and cell survival through the neuregulin-mediated PI 3-kinase signaling pathway...
  60. Yang Y, Wang H, Zhang J, Luo F, Herrup K, Bibb J, et al. Cyclin dependent kinase 5 is required for the normal development of oligodendrocytes and myelin formation. Dev Biol. 2013;378:94-106 pubmed publisher
    ..Cyclin dependent kinase 5 (Cdk5) and its co-activators play critical roles in the regulation of neuronal differentiation, cortical lamination, ..
  61. Moy L, Tsai L. Cyclin-dependent kinase 5 phosphorylates serine 31 of tyrosine hydroxylase and regulates its stability. J Biol Chem. 2004;279:54487-93 pubmed
    ..The proline-directed serine/threonine kinase cyclin-dependent kinase 5 (cdk5) plays an important role in diverse neuronal processes...
  62. Wong A, Lee R, Cheung A, Yeung P, Chung S, Cheung Z, et al. Cdk5-mediated phosphorylation of endophilin B1 is required for induced autophagy in models of Parkinson's disease. Nat Cell Biol. 2011;13:568-79 pubmed publisher
    Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase that is increasingly implicated in various neurodegenerative diseases...
  63. Sahin B, Hawasli A, Greene R, Molkentin J, Bibb J. Negative regulation of cyclin-dependent kinase 5 targets by protein kinase C. Eur J Pharmacol. 2008;581:270-5 pubmed publisher
    Cyclin-dependent kinase 5 (Cdk5) is a proline-directed protein serine/threonine kinase essential for brain development and implicated in synaptic plasticity, dopaminergic neurotransmission, drug addiction, and neurodegenerative disorders...
  64. Bankston A, Li W, Zhang H, Ku L, Liu G, Papa F, et al. p39, the primary activator for cyclin-dependent kinase 5 (Cdk5) in oligodendroglia, is essential for oligodendroglia differentiation and myelin repair. J Biol Chem. 2013;288:18047-57 pubmed publisher
    Cyclin-dependent kinase 5 (Cdk5) plays key roles in normal brain development and function. Dysregulation of Cdk5 may cause neurodegeneration and cognitive impairment...
  65. Takahashi S, Ohshima T, Cho A, Sreenath T, Iadarola M, Pant H, et al. Increased activity of cyclin-dependent kinase 5 leads to attenuation of cocaine-mediated dopamine signaling. Proc Natl Acad Sci U S A. 2005;102:1737-42 pubmed
    ..Cyclin-dependent kinase 5 (Cdk5) and its activator p35, proteins involved in phosphorylation of substrates in postmitotic neurons, have been found ..
  66. Gilmore E, Ohshima T, Goffinet A, Kulkarni A, Herrup K. Cyclin-dependent kinase 5-deficient mice demonstrate novel developmental arrest in cerebral cortex. J Neurosci. 1998;18:6370-7 pubmed
    The cerebral cortex of mice with a targeted disruption in the gene for cyclin-dependent kinase 5 (cdk5) is abnormal in its structure...
  67. Rashid T, Banerjee M, Nikolic M. Phosphorylation of Pak1 by the p35/Cdk5 kinase affects neuronal morphology. J Biol Chem. 2001;276:49043-52 pubmed
    The small GTPase Rac and its effectors, the Pak1 and p35/Cdk5 kinases, have been assigned important roles in regulating cytoskeletal dynamics in neurons...
  68. Ohshima T, Ogawa M, Veeranna -, Hirasawa M, Longenecker G, Ishiguro K, et al. Synergistic contributions of cyclin-dependant kinase 5/p35 and Reelin/Dab1 to the positioning of cortical neurons in the developing mouse brain. Proc Natl Acad Sci U S A. 2001;98:2764-9 pubmed
    Cyclin-dependent kinase (Cdk) 5 is a unique member of the Cdk family, because Cdk5 kinase activity is detected only in the nervous tissue. Two neuron-specific activating subunits of Cdk5, p35 and p39, have been identified...
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    Obesity induced in mice by high-fat feeding activates the protein kinase Cdk5 (cyclin-dependent kinase 5) in adipose tissues...
  70. Uchida Y, Ohshima T, Sasaki Y, Suzuki H, Yanai S, Yamashita N, et al. 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. 2005;10:165-79 pubmed
    ..In this study, we demonstrate that cyclin-dependent kinase 5 (Cdk5) and glycogen synthase kinase 3beta (GSK3beta) plays a critical role in Sema3A signalling...
  71. Van den Haute C, Spittaels K, Van Dorpe J, Lasrado R, Vandezande K, Laenen I, et al. Coexpression of human cdk5 and its activator p35 with human protein tau in neurons in brain of triple transgenic mice. Neurobiol Dis. 2001;8:32-44 pubmed
    The potential contribution of cyclin-dependent protein kinase 5 (cdk5) to hyperphosphorylate protein tau, as claimed in Alzheimer's disease, was investigated in vivo...
  72. Pareek T, Keller J, Kesavapany S, Agarwal N, Kuner R, Pant H, et al. Cyclin-dependent kinase 5 modulates nociceptive signaling through direct phosphorylation of transient receptor potential vanilloid 1. Proc Natl Acad Sci U S A. 2007;104:660-5 pubmed
    ..We have previously reported that cyclin-dependent kinase 5 (Cdk5) activity regulates nociceptive signaling...
  73. Lin L, Ye Y, Zakeri Z. p53, Apaf-1, caspase-3, and -9 are dispensable for Cdk5 activation during cell death. Cell Death Differ. 2006;13:141-50 pubmed
    Cyclin-dependent kinase 5 (Cdk5) is a member of the cyclin-dependent kinase family that is mostly seen in neurons, does not vary with cell cycle, and is activated in many neurodegenerative disorders and other non-neuronal pathologies, but ..