The p35/Cdk5 kinase is a neuron-specific Rac effector that inhibits Pak1 activity

Margareta Nikolic, Margaret M. Chou, Wange Lu, Bruce J. Mayer and Li-Huei Tsai ()
Additional contact information
Margareta Nikolic: Howard Hughes Medical Institute and Department of Pathology
Margaret M. Chou: Department of Cell Biology
Wange Lu: Harvard Medical School
Bruce J. Mayer: Harvard Medical School
Li-Huei Tsai: Howard Hughes Medical Institute and Department of Pathology

Nature, 1998, vol. 395, issue 6698, 194-198

Abstract: Abstract Cyclin-dependent kinase 5 (Cdk5) and its neuron-specific regulator p35 (refs 1–4) are essential for neuronal migration and for the laminar configuration of the cerebral cortex5,6,7. In addition, p35/Cdk5 kinase concentrates at the leading edges of axonal growth cones and regulates neurite outgrowth in cortical neurons in culture8. The Rho family of small GTPases is implicated in a range of cellular functions, including cell migration and neurite outgrowth9,10,11,12,13. Here we show that the p35/Cdk5 kinase co-localizes with Rac in neuronal growth cones. Furthermore, p35 associates directly with Rac in a GTP-dependent manner. Another Rac effector, Pak1 kinase14,15, is also present in the Rac–p35/Cdk5 complexes and co-localizes with p35/Cdk5 and Rac at neuronal peripheries. The active p35/Cdk5 kinase causes Pak1 hyperphosphorylation in a Rac-dependent manner, which results in downregulation of Pak1 kinase activity. Because the Rho family of GTPases and the Pak kinases are implicated in actin polymerization16,17,18, the modification of Pak1, imposed by the p35/Cdk5 kinase, is likely to have an impact on the dynamics of the reorganization of the actin cytoskeleton in neurons, thus promoting neuronal migration and neurite outgrowth.

Date: 1998
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/26034 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:395:y:1998:i:6698:d:10.1038_26034

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/26034

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().