Cyclin-dependent kinases in brain development and disease

Annual Review of Cell and Developmental Biology

Volumn 27, Issue , 2011, Pages 465-491

  Su, Susan C ^a   Tsai, Li Huei ^a  

^a HOWARD HUGHES MEDICAL INSTITUTE   (United States)

Author keywords

Alzheimer's disease; Cdk5; Epigenetics; Neurodegeneration; P25; P35; Synaptic homeostasis

Indexed keywords

BUTYROLACTONE; BUTYROLACTONE 1; CALPAIN; CYCLIN DEPENDENT KINASE 5; CYCLIN DEPENDENT KINASE 5 INHIBITOR; CYCLIN DEPENDENT KINASE INHIBITOR; GLUTAMIC ACID; OLOMOUCINE; PROTEIN P25; PROTEIN P35; PROTEIN P39; ROSCOVITINE; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; ARTICLE; BEHAVIOR; BRAIN DEVELOPMENT; BRAIN DISEASE; BRAIN ISCHEMIA; CELL MIGRATION; COGNITION; CORPUS STRIATUM; CYTOARCHITECTURE; DENDRITE; DOPAMINERGIC ACTIVITY; ENDOCYTOSIS; ENZYME ACTIVATION; ENZYME ACTIVITY; EPIGENETICS; EXOCYTOSIS; GENE CONTROL; GLUTAMATERGIC TRANSMISSION; HIPPOCAMPUS; HOMEOSTASIS; HUMAN; HUNTINGTON CHOREA; LEARNING; LONG TERM DEPRESSION; MEMORY; NERVE CELL; NERVE CELL DIFFERENTIATION; NERVE CELL PLASTICITY; NERVE FIBER; NERVE FIBER GROWTH; NEUROPATHOLOGY; NEUROTOXICITY; NEUROTRANSMISSION; NIEMANN PICK DISEASE; NONHUMAN; PARKINSON DISEASE; PRESYNAPTIC NERVE; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; SIGNAL TRANSDUCTION; STROKE; SYNAPSE VESICLE; SYNAPTIC TRANSMISSION;

ANIMALS; BRAIN; CELL MOVEMENT; CYCLIN-DEPENDENT KINASE 5; EPIGENESIS, GENETIC; HOMEOSTASIS; HUMANS; LEARNING; MEMORY; NERVE TISSUE PROTEINS; NEURITES; NEURODEGENERATIVE DISEASES; NEURONAL PLASTICITY; SYNAPTIC TRANSMISSION; SYNAPTIC VESICLES;

EID: 80054045373     PISSN: 10810706     EISSN: 15308995     Source Type: Book Series    
DOI: 10.1146/annurev-cellbio-092910-154023     Document Type: Article

References (192)

1. Ackerley S, Thornhill P, Grierson AJ, Brownlees J, Anderton BH, et al. 2003. Neurofilament heavy chain side arm phosphorylation regulates axonal transport of neurofilaments. J. Cell Biol. 161:489-95 (Pubitemid 36578574)
2. Adzic M, Djordjevic J, Djordjevic A, Niciforovic A, Demonacos C, et al. 2009. Acute or chronic stress induce cell compartment-specific phosphorylation of glucocorticoid receptor and alter its transcriptional activity in Wistar rat brain. J. Endocrinol. 202:87-97
3. Agarwal-Mawal A, PaudelHK. 2001. Neuronal Cdc2-like protein kinase (Cdk5/p25) is associated with protein phosphatase 1 and phosphorylates inhibitor-2. J. Biol. Chem. 276:23712-18
4. Ahlijanian MK, Barrezueta NX, Williams RD, Jakowski A, Kowsz KP, et al. 2000. Hyperphosphorylated tau and neurofilament and cytoskeletal disruptions in mice overexpressing human p25, an activator of cdk5. Proc. Natl. Acad. Sci. USA 97:2910-15 (Pubitemid 30159271)
5. Angelo M, Plattner F, Irvine EE, Giese KP. 2003. Improved reversal learning and altered fear conditioning in transgenic mice with regionally restricted p25 expression. Eur. J. Neurosci. 18:423-31 (Pubitemid 36999943)
6. Anne SL, Saudou F, Humbert S. 2007. Phosphorylation of huntingtin by cyclin-dependent kinase 5 is induced by DNA damage and regulates wild-type and mutant huntingtin toxicity in neurons. J. Neurosci. 27:7318-28 (Pubitemid 47037570)
7. Auer IA, Schmidt ML, Lee VM, Curry B, Suzuki K, et al. 1995. Paired helical filament tau (PHFtau) in Niemann-Pick type C disease is similar to PHFtau in Alzheimer's disease. Acta Neuropathol. 90:547-51
8. Avraham E, Rott R, Liani E, Szargel R, Engelender S. 2007. Phosphorylation of Parkin by the cyclindependent kinase 5 at the linker region modulates its ubiquitin-ligase activity and aggregation. J. Biol. Chem. 282:12842-50 (Pubitemid 47100582)
9. Baumann K, Mandelkow EM, Biernat J, Piwnica-Worms H, Mandelkow E. 1993. Abnormal Alzheimer-like phosphorylation of tau-protein by cyclin-dependent kinases cdk2 and cdk5. FEBS Lett. 336:417-24 (Pubitemid 24036992)
10. Beaudette KN, Lew J, Wang JH. 1993. Substrate specificity characterization of a cdc2-like protein kinase purified from bovine brain. J. Biol. Chem. 268:20825-30 (Pubitemid 23292256)
11. Bian F, Nath R, Sobocinski G, Booher RN, Lipinski WJ, et al. 2002. Axonopathy, tau abnormalities, and dyskinesia, but no neurofibrillary tangles in p25-transgenic mice. J. Comp. Neurol. 446:257-66 (Pubitemid 34246044)
12. Bibb JA, Chen J, Taylor JR, Svenningsson P, Nishi A, et al. 2001. Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5. Nature 410:376-80 (Pubitemid 32246055)
13. Bibb JA, Snyder GL, Nishi A, Yan Z, Meijer L, et al. 1999. Phosphorylation of DARPP-32 by Cdk5 modulates dopamine signalling in neurons. Nature 402:669-71 (Pubitemid 129516337)
14. Bliss TV P, Collingridge GL. 1993. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31-39 (Pubitemid 23020772)
15. Borrelli E, Nestler EJ, Allis CD, Sassone-Corsi P. 2008. Decoding the epigenetic language of neuronal plasticity. Neuron 60:961-74
16. Bowling AC, Schulz JB, Brown RH Jr, Beal MF. 1993. Superoxide dismutase activity, oxidative damage, and mitochondrial energy metabolism in familial and sporadic amyotrophic lateral sclerosis. J. Neurochem. 61:2322-25 (Pubitemid 23354097)
17. Brion JP, Couck AM. 1995. Cortical and brainstem-type Lewy bodies are immunoreactive for the cyclindependent kinase 5. Am. J. Pathol. 147:1465-76
18. BrownM, Jacobs T, Eickholt B, Ferrari G, Teo M, et al. 2004. α2-Chimaerin, cyclin-dependent kinase 5/p35, and its target collapsin response mediator protein-2 are essential components in semaphorin 3A-induced growth-cone collapse. J. Neurosci. 24:8994-9004 (Pubitemid 39372244)
19. Bu B, Li J, Davies P, Vincent I. 2002. Deregulation of cdk5, hyperphosphorylation, and cytoskeletal pathology in the Niemann-Pick type C murine model. J. Neurosci. 22:6515-25 (Pubitemid 35386408)
20. Cattaneo E, Rigamonti D, Goffredo D, Zuccato C, Squitieri F, Sipione S. 2001. Loss of normal huntingtin function: new developments in Huntington's disease research. Trends Neurosci. 24:182-88 (Pubitemid 32166824)
21. Chae T, Kwon YT, Bronson R, Dikkes P, Li E, Tsai LH. 1997. Mice lacking p35, a neuronal specific activator of Cdk5, display cortical lamination defects, seizures, and adult lethality. Neuron 18:29-42 (Pubitemid 27053828)
22. Cheng K, Li Z, Fu WY, Wang JH, Fu AK, Ip NY. 2002. Pctaire1 interacts with p35 and is a novel substrate for Cdk5/p35. J. Biol. Chem. 277:31988-93 (Pubitemid 34969008)
23. Chergui K, Svenningsson P, Greengard P. 2004. Cyclin-dependent kinase 5 regulates dopaminergic and glutamatergic transmission in the striatum. Proc. Natl. Acad. Sci. USA 101:2191-96 (Pubitemid 38229037)
24. Cheung ZH, Chin WH, Chen Y, Ng YP, Ip NY. 2007. Cdk5 is involved in BDNF-stimulated dendritic growth in hippocampal neurons. PLoS Biol. 5:e63
25. Choe EA, Liao L, Zhou JY, Cheng D, Duong DM, et al. 2007. Neuronal morphogenesis is regulated by the interplay between cyclin-dependent kinase 5 and the ubiquitin ligasemind bomb 1. J. Neurosci. 27:9503-12 (Pubitemid 47358202)
26. Choi JH, Banks AS, Estall JL, Kajimura S, Bostrom P, et al. 2010. Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARγby Cdk5. Nature 466:451-56
27. Connell-Crowley L, Le Gall M, Vo DJ, Giniger E. 2000. The cyclin-dependent kinase 5 Cdk5 controls multiple aspects of axon patterning in vivo. Curr. Biol. 10:599-602 (Pubitemid 30329446)
28. Connell-Crowley L, Vo D, Luke L, Giniger E. 2007. Drosophila lacking the Cdk5 activator, p35, display defective axon guidance, age-dependent behavioral deficits and reduced lifespan. Mech. Dev. 124:341-49 (Pubitemid 46509727)
29. Cruz JC, Kim D, Moy LY, Dobbin MM, Sun X, et al. 2006. p25/cyclin-dependent kinase 5 induces production and intraneuronal accumulation of amyloid βin vivo. J. Neurosci. 26:10536-41 (Pubitemid 44564604)
30. Cruz JC, Tseng HC, Goldman JA, Shih H, Tsai LH. 2003. Aberrant Cdk5 activation by p25 triggers pathological events leading to neurodegeneration and neurofibrillary tangles. Neuron 40:471-83 (Pubitemid 37494698)
31. De Vos KJ, Grierson AJ, Ackerley S, Miller CC. 2008. Role of axonal transport in neurodegenerative diseases. Annu. Rev. Neurosci. 31:151-73
32. Dhavan R, Greer PL, Morabito MA, Orlando LR, Tsai LH. 2002. The cyclin-dependent kinase 5 activators p35 and p39 interact with theα-subunit of Ca2+/calmodulin-dependent protein kinase II andα-actinin-1 in a calcium-dependent manner. J. Neurosci. 22:7879-91 (Pubitemid 35379093)
33. Dhavan R, Tsai LH. 2001. A decade of CDK5. Nat. Rev. Mol. Cell Biol. 2:749-59 (Pubitemid 33679837)
34. Elleder M, Jirasek A, Smid F, Ledvinova J, Besley GT. 1985. Niemann-Pick disease type C. Study on the nature of the cerebral storage process. Acta Neuropathol. 66:325-36 (Pubitemid 15005804)
35. Evans GJ, Cousin MA. 2007. Activity-dependent control of slow synaptic vesicle endocytosis by cyclindependent kinase 5. J. Neurosci. 27:401-11 (Pubitemid 46106014)
36. Feldmann G, Mishra A, Hong SM, Bisht S, Strock CJ, et al. 2010. Inhibiting the cyclin-dependent kinase CDK5 blocks pancreatic cancer formation and progression through the suppression of Ras-Ral signaling. Cancer Res. 70:4460-69
37. Fischer A, Sananbenesi F, Mungenast A, Tsai LH. 2010. Targeting the correct HDAC(s) to treat cognitive disorders. Trends Pharmacol. Sci. 31:605-17
38. FischerA, Sananbenesi F, Pang PT, Lu B, TsaiLH. 2005. Opposing roles of transient and prolonged expression of p25 in synaptic plasticity and hippocampus-dependent memory. Neuron 48:825-38 (Pubitemid 41759432)
39. Fischer A, Sananbenesi F, Wang X, Dobbin M, Tsai LH. 2007. Recovery of learning and memory is associated with chromatin remodelling. Nature 447:178-82 (Pubitemid 46763080)
40. Fletcher AI, Shuang R, Giovannucci DR, Zhang L, Bittner MA, Stuenkel EL. 1999. Regulation of exocytosis by cyclin-dependent kinase 5 via phosphorylation of Munc18. J. Biol. Chem. 274:4027-35
41. Floyd SR, Porro EB, Slepnev VI, Ochoa GC, Tsai LH, De Camilli P. 2001. Amphiphysin 1 binds the cyclindependent kinase (cdk) 5 regulatory subunit p35 and is phosphorylated by cdk5 and cdc2. J. Biol. Chem. 276:8104-10
42. Fu AK, Fu WY, Cheung J, Tsim KW, Ip FC, et al. 2001. Cdk5 is involved in neuregulin-induced AChR expression at the neuromuscular junction. Nat. Neurosci. 4:374-81 (Pubitemid 32260113)
43. Fu AK, Fu WY, Ng AK, Chien WW, Ng YP, et al. 2004. Cyclin-dependent kinase 5 phosphorylates signal transducer and activator of transcription 3 and regulates its transcriptional activity. Proc. Natl. Acad. Sci. USA 101:6728-33 (Pubitemid 38586042)
44. Fu AK, Ip FC, Fu WY, Cheung J, Wang JH, et al. 2005. Aberrant motor axon projection, acetylcholine receptor clustering, and neurotransmission in cyclin-dependent kinase 5 null mice. Proc. Natl. Acad. Sci. USA 102:15224-29 (Pubitemid 41513363)
45. Fu AK, Ip NY. 2007. Cyclin-dependent kinase 5 links extracellular cues to actin cytoskeleton during dendritic spine development. Cell Adh. Migr. 1:110-12
46. Fu WY, Chen Y, Sahin M, Zhao XS, Shi L, et al. 2007. Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanism. Nat. Neurosci. 10:67-76 (Pubitemid 46026529)
47. Glab N, Labidi B, Qin LX, Trehin C, Bergounioux C, Meijer L. 1994. Olomoucine, an inhibitor of the cdc2/cdk2 kinases activity, blocks plant cells at the G1 to S and G2 toMcell cycle transitions. FEBS Lett. 353:207-11 (Pubitemid 24319830)
48. Glicksman MA, Cuny GD, Liu M, Dobson B, Auerbach K, et al. 2007. New approaches to the discovery of cdk5 inhibitors. Curr. Alzheimer Res. 4:547-49 (Pubitemid 350248388)
49. Gong B, Wang H, Gu S, Heximer SP, Zhuo M. 2007. Genetic evidence for the requirement of adenylyl cyclase 1 in synaptic scaling of forebrain cortical neurons. Eur. J. Neurosci. 26:275-88 (Pubitemid 47087614)
50. Gong X, Tang X, Wiedmann M, Wang X, Peng J, et al. 2003. Cdk5-mediated inhibition of the protective effects of transcription factor MEF2 in neurotoxicity-induced apoptosis. Neuron 38:33-46 (Pubitemid 36423351)
51. Green SL, Kulp KS, VullietR. 1997. Cyclin-dependent protein kinase 5 activity increases in rat brain following ischemia. Neurochem. Int. 31:617-23 (Pubitemid 27375872)
52. Hallows JL, Iosif RE, Biasell RD, Vincent I. 2006. p35/p25 is not essential for tau and cytoskeletal pathology or neuronal loss in Niemann-Pick type C disease. J. Neurosci. 26:2738-44 (Pubitemid 43357857)
53. HamdaneM, Bretteville A, Sambo AV, Schindowski K, Begard S, et al. 2005. p25/Cdk5-mediated retinoblastoma phosphorylation is an early event in neuronal cell death. J. Cell Sci. 118:1291-98 (Pubitemid 40528698)
54. Harada T, Morooka T, Ogawa S, Nishida E. 2001. ERK induces p35, a neuron-specific activator of Cdk5, through induction of Egr1. Nat. Cell Biol. 3:453-59 (Pubitemid 32422080)
55. Hardy J, Selkoe DJ. 2002. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297:353-56 (Pubitemid 34790756)
56. Hashiguchi M, Saito T, Hisanaga S, Hashiguchi T. 2002. Truncation ofCDK5 activator p35 induces intensive phosphorylation of Ser202/Thr205 of human tau. J. Biol. Chem. 277:44525-30 (Pubitemid 36157887)
57. Hawasli AH, Benavides DR, Nguyen C, Kansy JW, Hayashi K, et al. 2007. Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control of NMDAR degradation. Nat. Neurosci. 10:880-86 (Pubitemid 47018172)
58. Hayashi T, Warita H, Abe K, Itoyama Y. 1999. Expression of cyclin-dependent kinase 5 and its activator p35 in rat brain after middle cerebral artery occlusion. Neurosci. Lett. 265:37-40 (Pubitemid 29210192)
59. Hirasawa M, Ohshima T, Takahashi S, Longenecker G, Honjo Y, et al. 2004. Perinatal abrogation of Cdk5 expression in brain results in neuronal migration defects. Proc. Natl. Acad. Sci. USA 101:6249-54 (Pubitemid 38520560)
60. Hou Z, He L, Qi RZ. 2007. Regulation of s6 kinase 1 activation by phosphorylation at ser-411. J. Biol. Chem. 282:6922-28 (Pubitemid 47093644)
61. Huang C, Rajfur Z, Yousefi N, Chen Z, Jacobson K, Ginsberg MH. 2009. Talin phosphorylation by Cdk5 regulates Smurf1-mediated talin head ubiquitylation and cell migration. Nat. Cell Biol. 11:624-30
62. Huang E, Qu D, Zhang Y, Venderova K, Haque ME, et al. 2010. The role of Cdk5-mediated apurinic/apyrimidinic endonuclease 1 phosphorylation in neuronal death. Nat. Cell Biol. 12:563-71
63. Humbert S, Dhavan R, Tsai LH. 2000a. p39 activates Cdk5 in neurons, and is associated with the actin cytoskeleton. J. Cell Sci. 113:975-83 (Pubitemid 30179477)
64. Humbert S, Lanier LM, Tsai LH. 2000b. Synaptic localization of p39, a neuronal activator of cdk5. Neuroreport 11:2213-16 (Pubitemid 30485564)
65. Iijima K, Ando K, Takeda S, Satoh Y, Seki T, et al. 2000. Neuron-specific phosphorylation of Alzheimer's β-amyloid precursor protein by cyclin-dependent kinase 5. J. Neurochem. 75:1085-91 (Pubitemid 30660497)
66. Ishizuka K, Kamiya A, Oh EC, Kanki H, Seshadri S, et al. 2011. DISC1-dependent switch from progenitor proliferation to migration in the developing cortex. Nature 473:92-96
67. Jessberger S, Aigner S, Clemenson GD Jr, Toni N, Lie DC, et al. 2008. Cdk5 regulates accurate maturation of newborn granule cells in the adult hippocampus. PLoS Biol. 6:e272
68. Juo P, Harbaugh T, Garriga G, Kaplan JM. 2007. CDK-5 regulates the abundance of GLR-1 glutamate receptors in the ventral cord of Caenorhabditis elegans. Mol. Biol. Cell 18:3883-93 (Pubitemid 47519481)
69. Kansy JW, Daubner SC, Nishi A, Sotogaku N, Lloyd MD, et al. 2004. Identification of tyrosine hydroxylase as a physiological substrate for Cdk5. J. Neurochem. 91:374-84 (Pubitemid 39363436)
70. Kato G, Maeda S. 1999. Neuron-specific Cdk5 kinase is responsible for mitosis-independent phosphorylation of c-Src at Ser75 in human Y79 retinoblastoma cells. J. Biochem. 126:957-61
71. Kawauchi T, Chihama K, Nabeshima Y, Hoshino M. 2006. Cdk5 phosphorylates and stabilizes p27kip1 contributing to actin organization and cortical neuronal migration. Nat. Cell Biol. 8:17-26 (Pubitemid 43064793)
72. Kesavapany S, Amin N, Zheng YL, Nijhara R, Jaffe H, et al. 2004. p35/cyclin-dependent kinase 5 phosphorylation of ras guanine nucleotide releasing factor 2 (RasGRF2) mediates Rac-dependent extracellular signal-regulated kinase 1/2 activity, altering RasGRF2 andmicrotubule-associated protein 1b distribution in neurons. J. Neurosci. 24:4421-31 (Pubitemid 38608153)
73. Kesavapany S, Lau KF, McLoughlin DM, Brownlees J, Ackerley S, et al. 2001. p35/cdk5 binds and phosphorylates β-catenin and regulates β-catenin/presenilin-1 interaction. Eur. J. Neurosci. 13:241-47 (Pubitemid 32142468)
74. Keshvara L, Magdaleno S, Benhayon D, Curran T. 2002. Cyclin-dependent kinase 5 phosphorylates disabled 1 independently of Reelin signaling. J. Neurosci. 22:4869-77 (Pubitemid 37465602)
75. Kim D, Frank CL, Dobbin MM, Tsunemoto RK, Tu W, et al. 2008. Deregulation of HDAC1 by p25/Cdk5 in neurotoxicity. Neuron 60:803-17
76. Kim D, Nguyen MD, Dobbin MM, Fischer A, Sananbenesi F, et al. 2007. SIRT1 deacetylase protects against neurodegeneration in models forAlzheimer's disease and amyotrophic lateral sclerosis. EMBOJ. 26:3169-79 (Pubitemid 47057498)
77. Kim SH, Ryan TA. 2010. CDK5 serves as a major control point in neurotransmitter release. Neuron 67:797-809
78. Kim Y, Sung JY, Ceglia I, Lee KW, Ahn JH, et al. 2006. Phosphorylation of WAVE1 regulates actin polymerization and dendritic spine morphology. Nature 442:814-17 (Pubitemid 44258911)
79. Kino T, Ichijo T, Amin ND, Kesavapany S, Wang Y, et al. 2007. Cyclin-dependent kinase 5 differentially regulates the transcriptional activity of the glucocorticoid receptor through phosphorylation: clinical implications for the nervous system response to glucocorticoids and stress. Mol. Endocrinol. 21:1552-68 (Pubitemid 47001081)
80. Ko J, Humbert S, Bronson RT, Takahashi S, Kulkarni AB, et al. 2001. p35 and p39 are essential for cyclindependent kinase 5 function during neurodevelopment. J. Neurosci. 21:6758-71 (Pubitemid 32781119)
81. Kobayashi S, Ishiguro K, Omori A, Takamatsu M, Arioka M, et al. 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 Lett. 335:171-75 (Pubitemid 23350401)
82. Kwiatkowski TJ Jr, Bosco DA, Leclerc AL, Tamrazian E, Vanderburg CR, et al. 2009. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 323:1205-8
83. Kwon YT, Gupta A, Zhou Y, Nikolic M, Tsai LH. 2000. Regulation of N-cadherin-mediated adhesion by the p35-Cdk5 kinase. Curr. Biol. 10:363-72 (Pubitemid 30213382)
84. Lagace DC, Benavides DR, Kansy JW, Mapelli M, Greengard P, et al. 2008. Cdk5 is essential for adult hippocampal neurogenesis. Proc. Natl. Acad. Sci. USA 105:18567-71
85. Lee KY, Helbing CC, Choi KS, Johnston RN, Wang JH. 1997. Neuronal Cdc2-like kinase (Nclk) binds and phosphorylates the retinoblastoma protein. J. Biol. Chem. 272:5622-26 (Pubitemid 27102388)
86. Lee MS, Kao SC, Lemere CA, Xia W, Tseng HC, et al. 2003. APP processing is regulated by cytoplasmid phosphorylation. J. Cell Biol. 163:83-95 (Pubitemid 37271436)
87. Lee MS, Kwon YT, Li M, Peng J, Friedlander RM, Tsai LH. 2000. Neurotoxicity induces cleavage of p35 to p25 by calpain. Nature 405:360-64 (Pubitemid 30337070)
88. Lee SY, Wenk MR, Kim Y, Nairn AC, De Camilli P. 2004. Regulation of synaptojanin 1 by cyclin-dependent kinase 5 at synapses. Proc. Natl. Acad. Sci. USA 101:546-51 (Pubitemid 38084673)
89. Lee SY, Voronov S, Letinic K, Nairn AC, Di Paolo G, De Camilli P. 2005. Regulation of the interaction between PIPKI gamma and talin by proline-directed protein kinases. J. Cell Biol. 168:789-99 (Pubitemid 40328162)
90. Lew J, Beaudette K, Litwin CM, Wang JH. 1992. Purification and characterization of a novel proline-directed protein kinase from bovine brain. J. Biol. Chem. 267:13383-90
91. Lew J, Huang QQ, Qi Z, Winkfein RJ, Aebersold R, et al. 1994. A brain-specific activator of cyclin-dependent kinase 5. Nature 371:423-26 (Pubitemid 24302557)
92. Li BS, Sun MK, Zhang L, Takahashi S, Ma W, et al. 2001. Regulation ofNMDAreceptors by cyclin-dependent kinase-5. Proc. Natl. Acad. Sci. USA 98:12742-47
93. Li BS, Zhang L, Takahashi S, Ma W, Jaffe H, et al. 2002. Cyclin-dependent kinase 5 prevents neuronal apoptosis by negative regulation of c-Jun N-terminal kinase 3. EMBO J. 21:324-33 (Pubitemid 34137294)
94. Li Z, David G, Hung KW, DePinho RA, Fu AK, Ip NY. 2004. Cdk5/p35 phosphorylates mSds3 and regulates mSds3-mediated repression of transcription. J. Biol. Chem. 279:54438-44 (Pubitemid 40053183)
95. Liang S, Wei FY, Wu YM, Tanabe K, Abe T, et al. 2007. Major Cdk5-dependent phosphorylation sites of amphiphysin 1 are implicated in the regulation of the membrane binding and endocytosis. J. Neurochem. 102:1466-76 (Pubitemid 47256188)
96. Lisman J, Schulman H, Cline H. 2002. The molecular basis of CaMKII function in synaptic and behavioural memory. Nat. Rev. Neurosci. 3:175-90 (Pubitemid 135706588)
97. Luo S, Vacher C, Davies JE, Rubinsztein DC. 2005. Cdk5 phosphorylation of huntingtin reduces its cleavage by caspases: implications for mutant huntingtin toxicity. J. Cell Biol. 169:647-56 (Pubitemid 41002857)
98. Ma XM, Kiraly DD, Gaier ED, Wang Y, Kim EJ, et al. 2008. Kalirin-7 is required for synaptic structure and function. J. Neurosci. 28:12368-82
99. Maestre C, Delgado-Esteban M, Gomez-Sanchez JC, Bolanos JP, Almeida A. 2008. Cdk5 phosphorylates Cdh1 and modulates cyclin B1 stability in excitotoxicity. EMBO J. 27:2736-45
100. Malenka RC, Bear MF. 2004. LTP and LTD: an embarrassment of riches. Neuron 44:5-21 (Pubitemid 39348827)
101. Mandelkow EM, Mandelkow E. 1998. Tau in Alzheimer's disease. Trends Cell Biol. 8:425-27 (Pubitemid 28529713)
102. MaoD, Hinds PW. 2010. p35 is required for CDK5 activation in cellular senescence. J. Biol. Chem. 285:4671-80
103. Matsubara M, Kusubata M, Ishiguro K, Uchida T, Titani K, Taniguchi H. 1996. Site-specific phosphorylation of synapsin I by mitogen-activated protein kinase and Cdk5 and its effects on physiological functions. J. Biol. Chem. 271:21108-13 (Pubitemid 26292961)
104. Matsuura I, Wang JH. 1996. Demonstration of cyclin-dependent kinase inhibitory serine/threonine kinase in bovine thymus. J. Biol. Chem. 271:5443-50 (Pubitemid 26083877)
105. Mayford M, Bach ME, Huang YY, Wang L, Hawkins RD, Kandel ER. 1996. Control of memory formation through regulated expression of a CaMKII transgene. Science 274:1678-83 (Pubitemid 26414891)
106. Meijer L, Borgne A, Mulner O, Chong JP, Blow JJ, et al. 1997. Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases Cdc2, Cdk2 and Cdk5. Eur. J. Biochem. 243:527-36 (Pubitemid 27060443)
107. Meyerson M, Enders GH, Wu CL, Su LK, Gorka C, et al. 1992. A family of human Cdc2-related protein kinases. EMBO J. 11:2909-17
108. Miyamoto Y, Yamauchi J, Chan JR, Okada A, Tomooka Y, Hisanaga S, Tanoue A. 2007. Cdk5 regulates differentiation of oligodendrocyte precursor cells through the direction phosphorylation of paxillin. J. Cell Sci. 140:4355-66
109. Morabito MA, Sheng M, Tsai LH. 2004. Cyclin-dependent kinase 5 phosphorylates the N-terminal domain of the postsynaptic density protein PSD-95 in neurons. J. Neurosci. 24:865-76 (Pubitemid 38146597)
110. Moy LY, Tsai LH. 2004. Cyclin-dependent kinase 5 phosphorylates serine 31 of tyrosine hydroxylase and regulates its stability. J. Biol. Chem. 279:54487-93 (Pubitemid 40053189)
111. Muntane G, Dalfo E, Martinez A, Ferrer I. 2008. Phosphorylation of tau and α-synuclein in synapticenriched fractions of the frontal cortex in Alzheimer's disease, and in Parkinson's disease and related α- synucleinopathies. Neuroscience 152:913-23
112. Murthy VN, De Camilli P. 2003. Cell biology of the presynaptic terminal. Annu. Rev. Neurosci. 26:701-28 (Pubitemid 37064948)
113. Muyllaert D, Terwe D, Kremer A, Snnvik K, Borghgraef P, et al. 2008. Neurodegeneration and neuroinflammation in Cdk5/p25-inducible mice: a model for hippocampal sclerosis and neocortical degeneration. Am. J. Pathol. 172:470-85 (Pubitemid 351282033)
114. Nakamura S, Kawamoto Y, Nakano S, Akiguchi I, Kimura J. 1997. p35nck5a and cyclin-dependent kinase 5 colocalize in Lewy bodies of brains with Parkinson's disease. Acta Neuropathol. 94:153-57 (Pubitemid 27338503)
115. Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, et al. 2006. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314:130-33 (Pubitemid 44547757)
116. Nguyen C, Bibb JA. 2003. Cdk5 and the mystery of synaptic vesicle endocytosis. J. Cell Biol. 163:697-99 (Pubitemid 37517876)
117. Nguyen C, Nishi A, Kansy JW, Fernandez J, Hayashi K, et al. 2007. Regulation of protein phosphatase inhibitor-1 by cyclin-dependent kinase 5. J. Biol. Chem. 282:16511-20 (Pubitemid 47100396)
118. Nguyen MD, Lariviere RC, Julien JP. 2001. Deregulation ofCdk5 in a mousemodel of ALS: toxicity alleviated by perikaryal neurofilament inclusions. Neuron 30:135-47 (Pubitemid 32441682)
119. NiethammerM, Smith DS, Ayala R, Peng J, Ko J, et al. 2000. NUDELis a novel Cdk5 substrate that associates with LIS1 and cytoplasmic dynein. Neuron 28:697-711 (Pubitemid 32038065)
120. Nikolic M, Chou MM, Lu W, Mayer BJ, Tsai LH. 1998. The p35/Cdk5 kinase is a neuron-specific Rac effector that inhibits Pak1 activity. Nature 395:194-98 (Pubitemid 28425661)
121. Nikolic M, Dudek H, Kwon YT, Ramos YF, Tsai LH. 1996. The Cdk5/p35 kinase is essential for neurite outgrowth during neuronal differentiation. Genes Dev. 10:816-25 (Pubitemid 26114738)
122. NobleW, Olm V, Takata K, Casey E, Mary O, et al. 2003. Cdk5 is a key factor in tau aggregation and tangle formation in vivo. Neuron 38:555-65 (Pubitemid 36645031)
123. Ohshima T, Ogura H, Tomizawa K, Hayashi K, Suzuki H, et al. 2005. Impairment of hippocampal long-term depression and defective spatial learning and memory in p35 mice. J. Neurochem. 94:917-25 (Pubitemid 41170580)
124. Ohshima T, Ward JM, Huh CG, Longenecker G, Veeranna, et al. 1996. Targeted disruption of the cyclindependent kinase 5 gene results in abnormal corticogenesis, neuronal pathology and perinatal death. Proc. Natl. Acad. Sci. USA 93:11173-78 (Pubitemid 26333137)
125. Olanow CW, Tatton WG. 1999. Etiology and pathogenesis of Parkinson's disease. Annu. Rev. Neurosci. 22:123-44 (Pubitemid 29144883)
126. Otth C, Concha II, Arendt T, Stieler J, Schliebs R, et al. 2002. AβPP induces Cdk5-dependent tau hyperphosphorylation in transgenic mice Tg2576. J. Alzheimers Dis. 4:417-30 (Pubitemid 35397807)
127. Ou CY, Poon VY, Maeder CI, Watanabe S, Lehrman EK, et al. 2010. Two cyclin-dependent kinase pathways are essential for polarized trafficking of presynaptic components. Cell 141(5):846-58
128. Paglini G, Pigino G, Kunda P, Morfini G, Maccioni R, et al. 1998. Evidence for the participation of the neuron-specific CDK5 activator P35 during laminin-enhanced axonal growth. J. Neurosci. 18:9858-69 (Pubitemid 28543764)
129. Paoletti P, Vila I, Rife M, Lizcano JM, Alberch J, Gines S. 2008. Dopaminergic and glutamatergic signaling crosstalk in Huntington's disease neurodegeneration: the role of p25/cyclin-dependent kinase 5. J. Neurosci. 28:10090-101
130. Pareek TK, Keller J, Kesavapany S, Agarwal N, Kuner R, et al. 2007. Cyclin-dependent kinase 5 modulates nociceptive signaling through direct phosphorylation of transient receptor potential vanilloid 1. Proc. Natl. Acad. Sci. USA 104:660-65 (Pubitemid 46123081)
131. Pareek TK, Keller J, Kesavapany S, Pant HC, Iadarola MJ, et al. 2006. Cyclin-dependent kinase 5 activity regulates pain signaling. Proc. Natl. Acad. Sci. USA 103:791-96 (Pubitemid 43153104)
132. Patrick GN, Zhou P, Kwon YT, Howley PM, Tsai LH. 1998. p35, the neuronal-specific activator of cyclindependent kinase 5 (Cdk5) is degraded by the ubiquitin-proteasome pathway. J. Biol. Chem. 273:24057-64 (Pubitemid 28435748)
133. 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 402:615-22 (Pubitemid 129516324)
134. Paudel HK, Lew J, Ali Z, Wang JH. 1993. Brain proline-directed protein kinase phosphorylates tau on sites that are abnormally phosphorylated in tau associated with Alzheimer's paired helical filaments. J. Biol. Chem. 268:23512-18 (Pubitemid 23328079)
135. Piedrahita D, Hernandez I, Lopez-Tobon A, Fedorov D, Obara B, et al. 2010. Silencing of CDK5 reduces neurofibrillary tangles in transgenic Alzheimer's mice. J. Neurosci. 30:13966-76
136. Pigino G, Paglini G, Ulloa L, Avila J, Caceres A. 1997. Analysis of the expression, distribution and function of cyclin dependent kinase 5 (Cdk5) in developing cerebellar macroneurons. J. Cell Sci. 110(Pt. 2):257-70 (Pubitemid 27075870)
137. Poon RY, Lew J, Hunter T. 1997. Identification of functional domains in the neuronal Cdk5 activator protein. J. Biol. Chem. 272:5703-8 (Pubitemid 27102398)
138. Poore CP, Sundaram JR, Pareek TK, Fu A, Amin N, et al. 2010. Cdk5-mediated phosphorylation of δ-catenin regulates its localization and GluR2-mediated synaptic activity. J. Neurosci. 30:8457-67
139. Qi Z, Huang QQ, Lee KY, Lew J, Wang JH. 1995. Reconstitution of neuronal Cdc2-like kinase from bacteriaexpressed Cdk5 and an active fragment of the brain-specific activator. Kinase activation in the absence of Cdk5 phosphorylation. J. Biol. Chem. 270:10847-54
140. Qu D, Rashidian J, Mount MP, Aleyasin H, Parsanejad M, et al. 2007. Role of Cdk5-mediated phosphorylation of Prx2 in MPTP toxicity and Parkinson's disease. Neuron 55:37-52 (Pubitemid 46990825)
141. Rashidian J, Iyirhiaro G, Aleyasin H, Rios M, Vincent I, et al. 2005. Multiple cyclin-dependent kinases signals are critical mediators of ischemia/hypoxic neuronal death in vitro and in vivo. Proc. Natl. Acad. Sci. USA 102:14080-85 (Pubitemid 41377706)
142. Rashidian J, Rousseaux MW, Venderova K, Qu D, Callaghan SM, et al. 2009. Essential role of cytoplasmic Cdk5 and Prx2 in multiple ischemic injury models, in vivo. J. Neurosci. 29:12497-505
143. Rutherford LC, Nelson SB, Turrigiano GG. 1998. BDNF has opposite effects on the quantal amplitude of pyramidal neuron and interneuron excitatory synapses. Neuron 21:521-30 (Pubitemid 28475504)
144. Samuels BA, Hsueh YP, Shu T, Liang H, Tseng HC, et al. 2007. Cdk5 promotes synaptogenesis by regulating the subcellular distribution of the MAGUK family member CASK. Neuron 56:823-37 (Pubitemid 350181349)
145. Sasaki S, Shionoya A, Ishida M, Gambello MJ, Yingling J, et al. 2000. A LIS1/NUDEL/cytoplasmic dynein heavy chain complex in the developing and adult nervous system. Neuron 28:681-96 (Pubitemid 32038064)
146. Saito T, Konno T, Hosokawa T, Asada A, Ishiguro K, Hisanaga S. 2007. p25/cyclin-dependent kinase 5 promotes the progression of cell death in nucleus of endoplasmic reticulum-stressed neurons. J. Neurochem. 102:133-40 (Pubitemid 46906270)
147. Saura CA, Choi SY, Beglopoulos V, Malkani S, Zhang D, et al. 2004. Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration. Neuron 42:23-36 (Pubitemid 38456965)
148. Sawamura N, Gong JS, Garver WS, Heidenreich RA, Ninomiya H, et al. 2001. Site-specific phosphorylation of tau accompanied by activation ofmitogen-activated protein kinase (MAPK) in brains ofNiemann-Pick type C mice. J. Biol. Chem. 276:10314-19
149. Schubert S, Knoch KP, Ouwendijk J, Mohammed S, Bodrov Y, et al. 2010. β2-Syntrophin is a Cdk5 substrate that restrains the motility of insulin secretory granules. PLoS ONE 5:e12929
150. Seeburg DP, Feliu-Mojer M, Gaiottino J, Pak DT, Sheng M. 2008. Critical role of CDK5 and Polo-like kinase 2 in homeostatic synaptic plasticity during elevated activity. Neuron 58:571-83 (Pubitemid 351681992)
151. Sharma P, Veeranna, Sharma M, Amin ND, Sihag RK, et al. 2002. Phosphorylation of MEK1 by cdk5/p35 down-regulates the mitogen-activated protein kinase pathway. J. Biol. Chem. 277:528-34 (Pubitemid 34952088)
152. Sheng M, Hoogenraad CC. 2007. The postsynaptic architecture of excitatory synapses: a more quantitative view. Annu. Rev. Biochem. 76:823-47
153. Shepherd JD, Rumbaugh G, Wu J, Chowdhury S, Plath N, et al. 2006. Arc/Arg3. 1 mediates homeostatic synaptic scaling of AMPA receptors. Neuron 52:475-84 (Pubitemid 44667431)
154. Shuang R, Zhang L, Fletcher A, Groblewski GE, Pevsner J, Stuenkel EL. 1998. Regulation of Munc-18/syntaxin 1A interaction by cyclin-dependent kinase 5 in nerve endings. J. Biol. Chem. 273:4957-66 (Pubitemid 28108649)
155. Singh KK, Ge X, Mao Y, Drane L, Meletis K, et al. 2010. Dixdc1 is a critical regulator of DISC1 and embryonic cortical development. Neuron 67:33-48
156. Small SA, Duff K. 2008. Linking Aβ and tau in late-onset Alzheimer's disease: a dual pathway hypothesis. Neuron 60:534-42
157. Smith DS, Greer PL, Tsai LH. 2001. Cdk5 on the brain. Cell Growth Differ. 12:277-83 (Pubitemid 32678219)
158. Smith PD, Crocker SJ, Jackson-Lewis V, Jordan-Sciutto KL, Hayley S, et al. 2003. Cyclin-dependent kinase 5 is a mediator of dopaminergic neuron loss in a mouse model of Parkinson's disease. Proc. Natl. Acad. Sci. USA 100:13650-55 (Pubitemid 37444794)
159. Smith PD, Mount MP, Shree R, Callaghan S, Slack RS, et al. 2006. Calpain-regulated p35/Cdk5 plays a central role in dopaminergic neuron death through modulation of the transcription factor myocyte enhancer factor 2. J. Neurosci. 26:440-47 (Pubitemid 43237108)
160. Sreedharan J, Blair IP, Tripathi VB, Hu X, Vance C, et al. 2008. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319:1668-72 (Pubitemid 351432505)
161. Sudhof TC. 2004. The synaptic vesicle cycle. Annu. Rev. Neurosci. 27:509-47 (Pubitemid 39050412)
162. Takahashi M, Iseki E, Kosaka K. 2000. Cyclin-dependent kinase 5 (Cdk5) associated with Lewy bodies in diffuse Lewy body disease. Brain Res. 862:253-56 (Pubitemid 30229795)
163. Takahashi S, Kulkarni AB. 2004. Mutant superoxide dismutase 1 causes motor neuron degeneration independent of cyclin-dependent kinase 5 activation by p35 or p25. J. Neurochem. 88:1295-304 (Pubitemid 38280697)
164. Takahashi S, Ohshima T, Hirasawa M, Pareek TK, Bugge TH, et al. 2010. Conditional deletion of neuronal cyclin-dependent kinase 5 in developing forebrain results inmicroglial activation and neurodegeneration. Am. J. Pathol. 176:320-29
165. Takashima A, Murayama M, Yasutake K, Takahashi H, Yokoyama M, Ishiguro K. 2001. Involvement of cyclin dependent kinase5 activator p25 on tau phosphorylation in mouse brain. Neurosci. Lett. 306:37-40 (Pubitemid 32524292)
166. Tan TC, Valova VA, Malladi CS, Graham ME, Berven LA, et al. 2003. Cdk5 is essential for synaptic vesicle endocytosis. Nat. Cell Biol. 5:701-10 (Pubitemid 36986777)
167. Tanaka T, Serneo FF, Tseng HC, Kulkarni AB, Tsai LH, Gleeson JG. 2004. Cdk5 phosphorylation of doublecortin ser297 regulates its effect on neuronal migration. Neuron 41:215-27 (Pubitemid 38125183)
168. Taniguchi M, Taoka M, Itakura M, Asada A, Saito T, et al. 2007. Phosphorylation of adult type Sept5 (CDCrel-1) by cyclin-dependent kinase 5 inhibits interaction with syntaxin-1. J. Biol. Chem. 282:7869-76 (Pubitemid 47093620)
169. Tang D, Yeung J, Lee KY, Matsushita M, Matsui H, et al. 1995. An isoform of the neuronal cyclin-dependent kinase 5 (Cdk5) activator. J. Biol. Chem. 270:26897-903
170. Tarricone C, Dhavan R, Peng J, Areces LB, Tsai LH, Musacchio A. 2001. Structure and regulation of the Cdk5-p25(nck5a) complex. Mol. Cell 8:657-69
171. Tian B, Yang Q, Mao Z. 2009. Phosphorylation of ATM by Cdk5 mediates DNA damage signalling and regulates neuronal death. Nat. Cell Biol. 11:211-18
172. Tomizawa K, Ohta J, Matsushita M, Moriwaki A, Li ST, et al. 2002. Cdk5/p35 regulates neurotransmitter release through phosphorylation and downregulation of P/Q-type voltage-dependent calcium channel activity. J. Neurosci. 22:2590-97 (Pubitemid 37465808)
173. Tomizawa K, Sunada S, Lu YF, Oda Y, Kinuta M, et al. 2003. Cophosphorylation of amphiphysin I and dynamin I by Cdk5 regulates clathrin-mediated endocytosis of synaptic vesicles. J. Cell Biol. 163:813-24 (Pubitemid 37517888)
174. Tsai LH, Delalle I, Caviness VS Jr, Chae T, Harlow E. 1994. p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5. Nature 371:419-23 (Pubitemid 24302556)
175. Tsai LH, Takahashi T, Caviness VS Jr, Harlow E. 1993. Activity and expression pattern of cyclin-dependent kinase 5 in the embryonic mouse nervous system. Development 119:1029-40 (Pubitemid 23358574)
176. Tseng HC, Zhou Y, Shen Y, Tsai LH. 2002. A survey of Cdk5 activator p35 and p25 levels in Alzheimer's disease brains. FEBS Lett. 523:58-62 (Pubitemid 34786058)
177. Turrigiano GG, Leslie KR, Desai NS, Rutherford LC, Nelson SB. 1998. Activity-dependent scaling of quantal amplitude in neocortical neurons. Nature 391:892-96 (Pubitemid 28157666)
178. Van Den Haute C, Spittaels K, Van Dorpe J, Lasrado R, Vandezande K, et al. 2001. Coexpression of human cdk5 and its activator p35 with human protein tau in neurons in brain of triple transgenic mice. Neurobiol. Dis. 8:32-44 (Pubitemid 32171816)
179. Vance C, Rogelj B, Hortobagyi T, De Vos KJ, Nishimura AL, et al. 2009. Mutations in FU S, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323:1208-11
180. Wang J, Liu S, Fu Y, Wang JH, Lu Y. 2003. Cdk5 activation induces hippocampal CA1 cell death by directly phosphorylating NMDA receptors. Nat. Neurosci. 6:1039-47 (Pubitemid 37186195)
181. Wei FY, Nagashima K, Ohshima T, Saheki Y, Lu YF, et al. 2005a. Cdk5-dependent regulation of glucosestimulated insulin secretion. Nat. Med. 11:1104-8 (Pubitemid 41486833)
182. Wei FY, Tomizawa K, Ohshima T, Asada A, Saito T, et al. 2005b. Control of cyclin-dependent kinase 5 (Cdk5) activity by glutamatergic regulation of p35 stability. J. Neurochem. 93:502-12 (Pubitemid 40547507)
183. Wen Y, Yang SH, Liu R, Perez EJ, Brun-Zinkernagel AM, et al. 2007. Cdk5 is involved in NFT-like tauopathy induced by transient cerebral ischemia in female rats. Biochim. Biophys. Acta 1772:473-83 (Pubitemid 46400382)
184. Wenzel HJ, Robbins CA, Tsai LH, Schwartzkroin PA. 2001. Abnormal morphological and functional organization of the hippocampus in a p35 mutant model of cortical dysplasia associated with spontaneous seizures. J. Neurosci. 21:983-98 (Pubitemid 32163139)
185. Xie Z, Sanada K, Samuels BA, Shih H, Tsai LH. 2003. Serine 732 phosphorylation of FAK by Cdk5 is important for microtubule organization, nuclear movement, and neuronal migration. Cell 114:469-82 (Pubitemid 37100995)
186. Xin X, Wang Y, Ma XM, Rompolas P, Keutmann HT, et al. 2008. Regulation of Kalirin by Cdk5. J. Cell Sci. 121:2601-11
187. Yan Z, Chi P, Bibb JA, Ryan TA, Greengard P. 2002. Roscovitine: a novel regulator of P/Q-type calcium channels and transmitter release in central neurons. J. Physiol. 540:761-70 (Pubitemid 35190150)
188. Zhang J, Krishnamurthy PK, Johnson GV. 2002. Cdk5 phosphorylates p53 and regulates its activity. J. Neurochem. 81:307-13 (Pubitemid 34809356)
189. Zhang M, Li J, Chakrabarty P, Bu B, Vincent I. 2004. Cyclin-dependent kinase inhibitors attenuate protein hyperphosphorylation, cytoskeletal lesion formation, and motor defects in Niemann-Pick type C mice. Am. J. Pathol. 165:843-53 (Pubitemid 39129292)
190. Zhang P, Yu PC, Tsang A HK, Chen Y, Fu A KY, et al. 2010. S-nitrosylation of cyclin-dependent kinase 5 (Cdk5) regulates its kinase activity and dendrite growth during neuronal development. J. Neurosci. 30:14366-70
191. Zhang S, Edelmann L, Liu J, Crandall JE, MorabitoMA. 2008. Cdk5 regulates the phosphorylation of tyrosine 1472 NR2B and the surface expression of NMDA receptors. J. Neurosci. 28:415-24
192. Zukerberg LR, Patrick GN, Nikolic M, Humbert S, Wu CL, et al. 2000. Cables links Cdk5 and c-Abl and facilitates Cdk5 tyrosine phosphorylation, kinase upregulation, and neurite outgrowth. Neuron 26:633-46