Cyclin-Dependent Kinase 5 (Cdk5) Modulates Signal Transduction Pathways Regulating Neuronal Survival

  • Parvathi Rudrabhatla
  • Jyotshna Kanungo
  • Ya-Li Zheng
  • Niranjana D. Amin
  • Sashi Kesavapany
  • Harish C. Pant


Cyclin-dependent kinase 5 (Cdk5) in the nervous system has evolved to become a “surveillance system” that, among its other functions, monitors and integrates fluctuations in the activities of signaling cascades involved in nervous system growth, differentiation, and survival. In this review, we have focused primarily on Cdk5 cross talk and neuronal survival conducted in our laboratory. Cdk5 activity is tightly regulated in the nervous system, but may be deregulated under neuronal stress such as oxidative injury, excitotoxic stimulations, and β-amyloid exposure resulting in apoptosis marked by aggregates of hyperphosphorylated Tau, neurofilament, and other cytoskeletal proteins. We have demonstrated that Cdk5 modulates mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK3), and phosphoinositol-3-kinase/protein kinase B (PI3 K/Akt). In addition, it is shown that Cdk5 directly and indirectly mediates the Ras guanine nucleotide exchange factors-1/2 (RasGRF1/2) and glycogen synthase kinase 3β (GSK3β) signaling pathways, respectively.


PC12 Cell Nerve Growth Factor Cortical Neuron Neuronal Survival Cytoskeletal Protein 
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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Parvathi Rudrabhatla
  • Jyotshna Kanungo
  • Ya-Li Zheng
  • Niranjana D. Amin
  • Sashi Kesavapany
  • Harish C. Pant
    • 1
  1. 1.Laboratory of NeurochemistryNational Institute of Neurological Disorders and Stroke, National Institutes of HealthBethesdaUSA

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