p35/Cyclin-dependent kinase 5 is required for protection against β-amyloid-induced cell death but not tau phosphorylation by ceramide

2007 ◽  
Vol 31 (1) ◽  
pp. 23-35 ◽  
Author(s):  
Kathleen I. Seyb ◽  
Sabah Ansar ◽  
Guibin Li ◽  
Jennifer Bean ◽  
Mary L. Michaelis ◽  
...  
Keyword(s):  
Cell Death ◽  
Tau Phosphorylation ◽  
Cyclin Dependent Kinase ◽  
Β Amyloid ◽  
Cyclin Dependent Kinase 5

scholarly journals Activation of Cyclin-Dependent Kinase 5 Is a Consequence of Cell Death

2009 ◽  
Vol 2009 ◽  
pp. 1-11 ◽  
Author(s):  
Yixia Ye ◽  
Antonella Tinari ◽  
Walter Malorni ◽  
Richard A. Lockshin ◽  
Zahra Zakeri
Keyword(s):  
Cell Death ◽  
Cell Division ◽  
Cell Differentiation ◽  
Metabolic Changes ◽  
Cyclin Dependent Kinase ◽  
Secondary Necrosis ◽  
Kinetics Of ◽  
Cyclin Dependent Kinase 5

Cyclin-dependent kinase 5 (Cdk5) is similar to other Cdks but is activated during cell differentiation and cell death rather than cell division. Since activation of Cdk5 has been reported in many situations leading to cell death, we attempted to determine if it was required for any form of cell death. We found that Cdk5 is activated during apoptotic deaths and that the activation can be detected even when the cells continue to secondary necrosis. This activation can occur in the absence of Bim, calpain, or neutral cathepsins. The kinase is typically activated by p25, derived from p35 by calpain-mediated cleavage, but inhibition of calpain does not affect cell death or the activation of Cdk5. Likewise, RNAi-forced suppression of the synthesis of Cdk5 does not affect the incidence or kinetics of cell death. We conclude that Cdk5 is activated as a consequence of metabolic changes that are common to many forms of cell death. Thus its activation suggests processes during cell death that will be interesting or important to understand, but activation of Cdk5 is not necessary for cells to die.

Cdk5 increases MARK4 activity and augments pathological tau accumulation and toxicity through tau phosphorylation at Ser262

2019 ◽  
Vol 28 (18) ◽  
pp. 3062-3071 ◽  
Author(s):  
Taro Saito ◽  
Toshiya Oba ◽  
Sawako Shimizu ◽  
Akiko Asada ◽  
Koichi M Iijima ◽  
...  
Keyword(s):  
Cultured Cells ◽  
Tau Phosphorylation ◽  
Activation Loop ◽  
Cyclin Dependent Kinase ◽  
Drosophila Model ◽  
Target Sites ◽  
Liver Kinase B1 ◽  
Tau Kinases ◽  
The Brain ◽  
Cyclin Dependent Kinase 5

Abstract Hyperphosphorylation of the microtubule-associated protein tau is associated with many neurodegenerative diseases, including Alzheimer’s disease. Microtubule affinity-regulating kinases (MARK) 1–4 and cyclin-dependent kinase 5 (Cdk5) are tau kinases under physiological and pathological conditions. However, their functional relationship remains elusive. Here, we report a novel mechanism by which Cdk5 activates MARK4 and augments tau phosphorylation, accumulation and toxicity. MARK4 is highly phosphorylated at multiple sites in the brain and in cultured neurons, and inhibition of Cdk5 activity reduces phosphorylation levels of MARK4. MARK4 is known to be activated by phosphorylation at its activation loop by liver kinase B1 (LKB1). In contrast, Cdk5 increased phosphorylation of MARK4 in the spacer domain, but not in the activation loop, and enhanced its kinase activity, suggesting a novel mechanism by which Cdk5 regulates MARK4 activity. We also demonstrated that co-expression of Cdk5 and MARK4 in mammalian cultured cells significantly increased the levels of tau phosphorylation at both Cdk5 target sites (SP/TP sites) and MARK target sites (Ser262), as well as the levels of total tau. Furthermore, using a Drosophila model of tau toxicity, we demonstrated that Cdk5 promoted tau accumulation and tau-induced neurodegeneration via increasing tau phosphorylation levels at Ser262 by a fly ortholog of MARK, Par-1. This study suggests a novel mechanism by which Cdk5 and MARK4 synergistically increase tau phosphorylation and accumulation, consequently promoting neurodegeneration in disease pathogenesis.

scholarly journals Tau Phosphorylation by Cyclin-dependent Kinase 5/p39 during Brain Development Reduces Its Affinity for Microtubules

2003 ◽  
Vol 278 (12) ◽  
pp. 10506-10515 ◽  
Author(s):  
Satoru Takahashi ◽  
Taro Saito ◽  
Shin-ichi Hisanaga ◽  
Harish C. Pant ◽  
Ashok B. Kulkarni
Keyword(s):  
Brain Development ◽  
Tau Phosphorylation ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase 5
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