Anita Terse1, Niranjana Amin2, Bradford Hall1, Manju Bhaskar2, Binukumar B K3, Elias Utreras4, Tej K Pareek5, Harish Pant2, Ashok B Kulkarni1. 1. National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland. 2. National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. 3. CSIR-Institute of Genomics and Integrative Biology (IGIB), New Delhi, India. 4. Department of Biology, Universidad de Chile, Santiago, Chile. 5. Celloram Inc., Beachwood, Ohio.
Abstract
Cyclin-dependent kinases (Cdks) are generally known to be involved in controlling the cell cycle, but Cdk5 is a unique member of this protein family for being most active in post-mitotic neurons. Cdk5 is developmentally important in regulating neuronal migration, neurite outgrowth, and axon guidance. Cdk5 is enriched in synaptic membranes and is known to modulate synaptic activity. Postnatally, Cdk5 can also affect neuronal processes such as dopaminergic signaling and pain sensitivity. Dysregulated Cdk5, in contrast, has been linked to neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Despite primarily being implicated in neuronal development and activity, Cdk5 has lately been linked to non-neuronal functions including cancer cell growth, immune responses, and diabetes. Since Cdk5 activity is tightly regulated, a method for measuring its kinase activity is needed to fully understand the precise role of Cdk5 in developmental and disease processes. This article includes methods for detecting Cdk5 kinase activity in cultured cells or tissues, identifying new substrates, and screening for new kinase inhibitors. Furthermore, since Cdk5 shares homology and substrate specificity with Cdk1 and Cdk2, the Cdk5 kinase assay can be used, with modification, to measure the activity of other Cdks as well.
Cyclin-dependent kinases (Cdks) are generally known to be involved in controlling the cell cycle, but Cdk5 is a unique member of this protein family for being most active in post-mitotic neurons. Cdk5 is developmentally important in regulating neuronal migration, neurite outgrowth, and axon guidance. Cdk5 is enriched in synaptic membranes and is known to modulate synaptic activity. Postnatally, Cdk5 can also affect neuronal processes such as dopaminergic signaling and pain sensitivity. Dysregulated Cdk5, in contrast, has been linked to neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Despite primarily being implicated in neuronal development and activity, Cdk5 has lately been linked to non-neuronal functions including cancer cell growth, immune responses, and diabetes. Since Cdk5 activity is tightly regulated, a method for measuring its kinase activity is needed to fully understand the precise role of Cdk5 in developmental and disease processes. This article includes methods for detecting Cdk5 kinase activity in cultured cells or tissues, identifying new substrates, and screening for new kinase inhibitors. Furthermore, since Cdk5 shares homology and substrate specificity with Cdk1 and Cdk2, the Cdk5 kinase assay can be used, with modification, to measure the activity of other Cdks as well.
Authors: K Ishiguro; S Kobayashi; A Omori; M Takamatsu; S Yonekura; K Anzai; K Imahori; T Uchida Journal: FEBS Lett Date: 1994-04-04 Impact factor: 4.124
Authors: Bradford E Hall; Michaela Prochazkova; Matthew R Sapio; Paul Minetos; Natalya Kurochkina; B K Binukumar; Niranjana D Amin; Anita Terse; John Joseph; Stephen J Raithel; Andrew J Mannes; Harish C Pant; Man-Kyo Chung; Michael J Iadarola; Ashok B Kulkarni Journal: Sci Rep Date: 2018-01-19 Impact factor: 4.379