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Gene Review

Cdk5  -  cyclin-dependent kinase 5

Rattus norvegicus

Synonyms: Cdkn5, Cell division protein kinase 5, Cyclin-dependent-like kinase 5, Serine/threonine-protein kinase PSSALRE, TPKII catalytic subunit, ...
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Disease relevance of Cdk5

  • Deregulation of the Cdk5 enzymatic activity was found to associate with a number of neurodegenerative diseases [1].
  • Hypoxia/reoxygenation alone reduced both the protein amount and activity of Cdk5, and this reduction was inhibited by pre-treatment with ASA [2].
  • Recently, the toxicity of Abeta to neurons was shown to be dependent upon the activation of cyclin-dependent kinase 5 (Cdk5), thought to promote tau phosphorylation that leads to cytoskeletal disruption, morphological degeneration and apoptosis [3].
  • An immunohistochemical study showed that Cdk5 was expressed in the ganglion cells and in some cells in the inner nuclear layer at an early stage [4].
  • The present results suggest that IGF-1 has a significant effect on ameliorating brain injury after transient focal brain ischemia with affecting the expressions of cdk5 and its activator p35 [5].

Psychiatry related information on Cdk5


High impact information on Cdk5


Chemical compound and disease context of Cdk5

  • Cyclin dependent kinase 5 (Cdk5) is a proline-direct protein kinase that is most active in the CNS, and has been implicated as a contributing factor in certain neurodegenerative diseases [11].

Biological context of Cdk5


Anatomical context of Cdk5

  • Together, these data suggest that control of the cortical actin cytoskeleton, long known to modulate hormone exocytosis and subsequent endocytosis, involves Cdk5-mediated activation of Trio [15].
  • L6 myoblast differentiation is modulated by Cdk5 via the PI3K-AKT-p70S6K signaling pathway [17].
  • Cdk5 and p35 are highly localized in the growth cone of cultured neurons, and Cdk5 activity is associated with neurite outgrowth [18].
  • Retardation of axonal regeneration by Cdk5 inhibition was confirmed by reduced labeling of facial motor neurons using retrograde tracer fluorogold (FG) [18].
  • Here we report evidence on the functional involvement of Cdk5 kinase in regenerating peripheral nerve fibers [18].

Associations of Cdk5 with chemical compounds

  • Neurotoxic insults deregulate Cdk5 activity, which leads to neuronal apoptosis and may contribute to neurodegeneration [12].
  • The complex of Cdk5 and its neuronal activator p35 is a proline-directed Ser/Thr kinase that plays an important role in various neuronal functions [1].
  • Hormone secretion by pituitary cells is decreased by roscovitine, an inhibitor of cyclin-dependent kinase 5 (Cdk5) [15].
  • Administration of Cdk5 inhibitors, roscovitine and olomoucine, into the crushed nerves resulted in decreases in Cdk5 kinase activity in nerves and retardation of nerve fiber regrowth [18].
  • The prevention of the loss in Cdk5 activity during reoxygenation was crucial for ASA-induced protection, because co-administration of Cdk5 inhibitors at the onset ofreoxygenation abolished the protection [2].

Physical interactions of Cdk5

  • Activity and regulation of p35/Cdk5 kinase complex [19].

Enzymatic interactions of Cdk5

  • Endophilin-SH3 binding to the high affinity site was disrupted when dynamin-1 PRD was phosphorylated with Cdk5, indicating that this site overlaps the phosphorylation sites, but amphiphysin-SH3 binding was unaffected [20].
  • Cdk5 phosphorylates CRMP-2 at serine 522, possibly facilitating phosphorylation of serine 518 and threonine 514 by glycogen synthase kinase 3beta (GSK3beta), a kinase previously implicated in Sema 3A signaling [21].
  • We conclude that cdk-5 and GSK-3 phosphorylate different residues or sets of residues within NF-H sidearm in cells [22].

Regulatory relationships of Cdk5


Other interactions of Cdk5


Analytical, diagnostic and therapeutic context of Cdk5


  1. Protein kinase CK2 is an inhibitor of the neuronal Cdk5 kinase. Lim, A.C., Hou, Z., Goh, C.P., Qi, R.Z. J. Biol. Chem. (2004) [Pubmed]
  2. Aspirin provides cyclin-dependent kinase 5-dependent protection against subsequent hypoxia/reoxygenation damage in culture. Vartiainen, N., Keksa-Goldsteine, V., Goldsteins, G., Koistinaho, J. J. Neurochem. (2002) [Pubmed]
  3. Amyloid-beta-induced toxicity of primary neurons is dependent upon differentiation-associated increases in tau and cyclin-dependent kinase 5 expression. Liu, T., Perry, G., Chan, H.W., Verdile, G., Martins, R.N., Smith, M.A., Atwood, C.S. J. Neurochem. (2004) [Pubmed]
  4. Developmental alteration of the expression and kinase activity of cyclin-dependent kinase 5 (Cdk5)/p35nck5a in the rat retina. Hirooka, K., Tomizawa, K., Matsui, H., Tokuda, M., Itano, T., Hasegawa, E., Wang, J.H., Hatase, O. J. Neurochem. (1996) [Pubmed]
  5. Insulin-like growth factor-1 affects expressions of cyclin-dependent kinase 5 and its activator p35 in reperfused rat brain. Wang, J.M., Hayashi, T., Zhang, W.R., Sakai, K., Shiro, Y., Abe, K. Neurosci. Lett. (1999) [Pubmed]
  6. Cdk5/p35 regulates neurotransmitter release through phosphorylation and downregulation of P/Q-type voltage-dependent calcium channel activity. Tomizawa, K., Ohta, J., Matsushita, M., Moriwaki, A., Li, S.T., Takei, K., Matsui, H. J. Neurosci. (2002) [Pubmed]
  7. Neuroadaptations of Cdk5 in cholinergic interneurons of the nucleus accumbens and prefrontal cortex of inbred alcohol-preferring rats following voluntary alcohol drinking. Camp, M.C., Mayfield, R.D., McCracken, M., McCracken, L., Alcantara, A.A. Alcohol. Clin. Exp. Res. (2006) [Pubmed]
  8. Cocaine-induced proliferation of dendritic spines in nucleus accumbens is dependent on the activity of cyclin-dependent kinase-5. Norrholm, S.D., Bibb, J.A., Nestler, E.J., Ouimet, C.C., Taylor, J.R., Greengard, P. Neuroscience (2003) [Pubmed]
  9. Cdk5 activation induces hippocampal CA1 cell death by directly phosphorylating NMDA receptors. Wang, J., Liu, S., Fu, Y., Wang, J.H., Lu, Y. Nat. Neurosci. (2003) [Pubmed]
  10. Cdk5 is involved in neuregulin-induced AChR expression at the neuromuscular junction. Fu, A.K., Fu, W.Y., Cheung, J., Tsim, K.W., Ip, F.C., Wang, J.H., Ip, N.Y. Nat. Neurosci. (2001) [Pubmed]
  11. Cdk5 phosphorylates p53 and regulates its activity. Zhang, J., Krishnamurthy, P.K., Johnson, G.V. J. Neurochem. (2002) [Pubmed]
  12. Cdk5-mediated inhibition of the protective effects of transcription factor MEF2 in neurotoxicity-induced apoptosis. Gong, X., Tang, X., Wiedmann, M., Wang, X., Peng, J., Zheng, D., Blair, L.A., Marshall, J., Mao, Z. Neuron (2003) [Pubmed]
  13. Cdk5 is essential for synaptic vesicle endocytosis. Tan, T.C., Valova, V.A., Malladi, C.S., Graham, M.E., Berven, L.A., Jupp, O.J., Hansra, G., McClure, S.J., Sarcevic, B., Boadle, R.A., Larsen, M.R., Cousin, M.A., Robinson, P.J. Nat. Cell Biol. (2003) [Pubmed]
  14. Regulation of synaptojanin 1 by cyclin-dependent kinase 5 at synapses. Lee, S.Y., Wenk, M.R., Kim, Y., Nairn, A.C., De Camilli, P. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  15. Cdk5 and Trio modulate endocrine cell exocytosis. Xin, X., Ferraro, F., Bäck, N., Eipper, B.A., Mains, R.E. J. Cell. Sci. (2004) [Pubmed]
  16. Cdk5-mediated phosphorylation of Axin directs axon formation during cerebral cortex development. Fang, W.Q., Ip, J.P., Li, R., Ng, Y.P., Lin, S.C., Chen, Y., Fu, A.K., Ip, N.Y. J. Neurosci. (2011) [Pubmed]
  17. L6 myoblast differentiation is modulated by Cdk5 via the PI3K-AKT-p70S6K signaling pathway. Sarker, K.P., Lee, K.Y. Oncogene (2004) [Pubmed]
  18. Activation of cyclin-dependent kinase 5 is involved in axonal regeneration. Namgung, U., Choi, B.H., Park, S., Lee, J.U., Seo, H.S., Suh, B.C., Kim, K.T. Mol. Cell. Neurosci. (2004) [Pubmed]
  19. Activity and regulation of p35/Cdk5 kinase complex. Nikolic, M., Tsai, L.H. Meth. Enzymol. (2000) [Pubmed]
  20. Kinetics of Src homology 3 domain association with the proline-rich domain of dynamins: specificity, occlusion, and the effects of phosphorylation. Solomaha, E., Szeto, F.L., Yousef, M.A., Palfrey, H.C. J. Biol. Chem. (2005) [Pubmed]
  21. Alpha2-chimaerin, cyclin-dependent Kinase 5/p35, and its target collapsin response mediator protein-2 are essential components in semaphorin 3A-induced growth-cone collapse. Brown, M., Jacobs, T., Eickholt, B., Ferrari, G., Teo, M., Monfries, C., Qi, R.Z., Leung, T., Lim, L., Hall, C. J. Neurosci. (2004) [Pubmed]
  22. Differential cellular phosphorylation of neurofilament heavy side-arms by glycogen synthase kinase-3 and cyclin-dependent kinase-5. Guidato, S., Tsai, L.H., Woodgett, J., Miller, C.C. J. Neurochem. (1996) [Pubmed]
  23. Molecular characterization of a neuronal-specific protein that stimulates the activity of Cdk5. Shetty, K.T., Kaech, S., Link, W.T., Jaffe, H., Flores, C.M., Wray, S., Pant, H.C., Beushausen, S. J. Neurochem. (1995) [Pubmed]
  24. A specific interaction between muskelin and the cyclin-dependent kinase 5 activator p39 promotes peripheral localization of muskelin. Ledee, D.R., Gao, C.Y., Seth, R., Fariss, R.N., Tripathi, B.K., Zelenka, P.S. J. Biol. Chem. (2005) [Pubmed]
  25. Both N-methyl-D-aspartate (NMDA) and non-NMDA receptors mediate glutamate-induced cleavage of the cyclin-dependent kinase 5 (cdk5) activator p35 in cultured rat hippocampal neurons. Kerokoski, P., Suuronen, T., Salminen, A., Soininen, H., Pirttilä, T. Neurosci. Lett. (2004) [Pubmed]
  26. Induction of Cdk5 activity in rat skeletal muscle after nerve injury. Fu, W.Y., Fu, A.K., Lok, K.C., Ip, F.C., Ip, N.Y. Neuroreport (2002) [Pubmed]
  27. Neuronal migration is transiently delayed by prenatal exposure to intermittent hypoxia. Zechel, J.L., Gamboa, J.L., Peterson, A.G., Puchowicz, M.A., Selman, W.R., Lust, W.D. Birth Defects Res. B Dev. Reprod. Toxicol. (2005) [Pubmed]
  28. Very low levels of methylmercury induce cell death of cultured rat cerebellar neurons via calpain activation. Sakaue, M., Okazaki, M., Hara, S. Toxicology (2005) [Pubmed]
  29. The effect of 'binge' cocaine administration on the expression of cyclin-dependent kinase 5 and its activator p35 in various regions of rat brain. Wedzony, K., Markowicz-Kula, K., Chocyk, A., Fijał, K., Maćkowiak, M. Brain Res. (2005) [Pubmed]
  30. The levels of cdk5 and p35 proteins and tau phosphorylation are reduced during neuronal apoptosis. Kerokoski, P., Suuronen, T., Salminen, A., Soininen, H., Pirttilä, T. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
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