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Cdk5 and Neuregulin-1 Signaling

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Cyclin Dependent Kinase 5 (Cdk5)

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Abstract

Cyclin-dependent kinase 5 (cdk5) is implicated in many neurodegenerative diseases including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson’s disease (PD). Overexpression of p25 in transgenic mice leads to enhanced cdk5 activity, together with aberrant phosphorylation of cytoskeletal components and the formation of hyperphosphorylated tau. Consistent with previous findings, we observed enhanced NRG-1/ErbB receptor signaling in the p25 overexpressing mice, together with increased PI3 kinase (P13 K)/Akt activity and GSK3β inhibition by S9 phosphorylation. Further, a specific cdk5 inhibitor CP-681301 reduces ErbB2 receptor tyrosine phosphorylation. These results imply that cdk5 is involved in neuregulin-dependent activation of the PI3 K/Akt neuronal survival pathway and potentially other NRG-1-related signaling pathways by regulating the phosphorylation of ErbB2/ErbB3.

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Author information

Authors and Affiliations

  1. Department of Pathology, Taub Institute for Alzheimer’s Disease research, Columbia University; NYS Psychiatric Institute, 10032, New York, USA

    Karen Duff

Authors
  1. Yi Wen
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  2. Haung Yu
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  3. Karen Duff
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Corresponding author

Correspondence to Karen Duff .

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Editors and Affiliations

  1. Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China

    Nancy Y. Ip

  2. Department of Brain and Cognitive Science, Howard Hughes Medical Institute, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 02139, Cambridge, MA, USA

    Li-Huei Tsai

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Wen, Y., Yu, H., Duff, K. (2008). Cdk5 and Neuregulin-1 Signaling. In: Ip, N.Y., Tsai, LH. (eds) Cyclin Dependent Kinase 5 (Cdk5). Springer, Boston, MA. https://doi.org/10.1007/978-0-387-78887-6_10

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