Neuronal cdc-2-like kinase (Nclk) has been shown to play an important role in a variety of cellular functions, including neuronal cell differentiation, neuro-migration, neuro-muscular junction signaling and apoptosis. The kinase consists of a catalytic subunit, Cdk5, and an essential activator, Nck5a or Nck5ai (p25^Nck5a, p35^Nck5a, or p39^Nck5ai). A variety of cellular proteins have been shown to associate with Nck5a. C42, C48 and C53 are these novel Nck5a-binding proteins isolated from the yeast two-hybrid screen. One of the clones, C42, has been shown to display Cdk5 kinase inhibition....[ Read more ]

Neuronal cdc-2-like kinase (Nclk) has been shown to play an important role in a variety of cellular functions, including neuronal cell differentiation, neuro-migration, neuro-muscular junction signaling and apoptosis. The kinase consists of a catalytic subunit, Cdk5, and an essential activator, Nck5a or Nck5ai (p25^Nck5a, p35^Nck5a, or p39^Nck5ai). A variety of cellular proteins have been shown to associate with Nck5a. C42, C48 and C53 are these novel Nck5a-binding proteins isolated from the yeast two-hybrid screen. One of the clones, C42, has been shown to display Cdk5 kinase inhibition.

The characterization of the cellular function of C42 was carried out in this study. Expression of the C42 protein in neuronal cell NG108-15 can prevent the cell from entering differentiation, indicating that C42 may be one of the physiological regulators of Nclk. In contrast, there is no significant effect on neuronal cell differentiation when another Nck5a-binding protein, C48, is expressed inside the cells. In addition, C42 maybe involved in apoptosis, since extensive cell death is observed upon the expression of C42 protein in cells.