Cyclin dependent kinase 5 phosphorylation of disabled 1 protein

A method for identifying a compound that inhibits or decreases Cdk5 activity which could be used for the treatment of a disease or condition where Cdk5 activity is involved in pathogenesis, which method comprises

• (a) determining whether Dab1 in a test sample is phosphorylated on a candidate sequence preferred by Cdk5 activity in the presence of said compound and active Cdk5 and
• (b) comparing Cdk5 activity in said test sample with Cdk5 activity in a control sample which contains active Cdk5 but lacks the compound, wherein decreased phosphorylation of Dab 1 in said test sample as compared to said control sample indicates a compound that is capable of inhibiting or decreasing Cdk5 activity.

A method for identifying a compound that increases Cdk5 activity which could be used for the treatment of a disease or condition in which Cdk5 activity is involved in pathogenesis, which method comprises

• (a) determining whether Dab1 in a test sample is phosphorylated on a candidate sequence preferred by Cdk5 activity in the presence of said compound and active Cdk5 and
• (b) comparing Cdk5 activity in said test sample with Cdk5 activity in a control sample which contains active Cdk5 but lacks the compound, wherein increased phosphorylation of Dab1 in said test sample as compared to said control sample indicates a compound that is capable of increasing Cdk5 activity.

A screening kit comprising

• (a) an antibody that binds to Dab1 only when it is phosphorylated on a candidate sequence preferred by Cdk5 activity;
• and
• (b) reagents suitable for detecting the binding of said antibody to Dab 1.

An antibody that binds to Dab1 only when it is phosphorylated on a candidate sequence preferred by Cdk5 activity.

A method for quantitating the level of cyclin dependent kinase 5 (Cdk5) activity in a biological sample, which method comprises

• (a) determining the amount of Disabled 1 protein (Dab1) in said sample which is phosphorylated on a candidate sequence preferred by Cdk 5 activity, and
• (b) determining the total amount of Dab1 in said sample, wherein the proportion of Dab1 which is is phosphorylated on said candidate sequence represents a quantitative measure of the level of Cdk5 activity in said sample.