Research Project
Grant-in-Aid for Scientific Research (C)
Purpose and Method :Cdk5 is a neuron-specific Ser/Thr protein kinase and Cdk5 KO mice exhibit defective brain development particularly in layer formation of cortical structures. Abnormalities of brain development in Cdk5 KO mice are caused by defects in the phosphorylations of brain development related-proteins. Using brains from Cdk5 KO mice, we conducted a screening to identify Cdk5 substrate(s). Functional analysis of newly identified substrate(s) is further performed. We also studied the functional significance of Cdk5-mediated phosphorylation of Dab1 which is a intracellular mediator of Reelin signaling.Results :Through the screening, we identified CRMP2 as a substrate of Cdk5. Under the collaboration with Dr.Goshima's group in Yokohama City University School of Medicine, we found Cdk5 phosphorylates CRMP2 at Ser522. This phosphorylation is required for Ser509 phosphorylation by GSK3β. This sequential phosphorylation by Cdk5 and GSK3β reduces the affinity between CRMP2 and tubulins. We also demonstrate that this sequential phosphorylation of CRMP2 is related to the production of 3F4 reactivity specifically in the brains from Alzheimer's patients. In another study, we showed that Cdk5 phosphorylates Dab1 at multiple sites in its C-terminal. Cdk5-mediated Ser/Thr phosphorylations of Dab1 inhibit tyrosine phosphorylation of Dab1 induced by Reelin. This result indicates a negative modulation of Reelin signaling by Cdk5.
All 2006 2005 Other
All Journal Article (10 results) Publications (1 results)
Brain Reserch (in press)
Brain Res. (in press)
Brain Research (in press)
Genes to Cells Vol.10,Issue 2
Pages: 165-179
J. Neurochem. 94
Pages: 917-925
Genes to Cells 10
J Neurochem. 94
J.Neurochem. 94
Nature Medicine 11
Pages: 1104-1108
Genes to Cells Vol.10, Issue 2
