Cables links Cdk5 and c-Abl and facilitates Cdk5 tyrosine phosphorylation,kinase upregulation, and neurite outgrowth

Cyclin-dependent kinase 5 (Cdk5) is a small serine/threonine kinase that pl ays a pivotal role during development of the CNS. Cables, a novel protein, interacts with Cdk5 in brain lysates. Cables also binds to and is a substra te of the c-Abl tyrosine kinase. Active c-Abl kinase leads to Cdk5 tyrosine phosphorylation, and this phosphorylation is enhanced by Cables. Phosphory lation of Cdk5 by c-Abl occurs on tyrosine 15 (Y15), which is stimulatory f or p35/Cdk5 kinase activity. Expression of antisense Cables in primary cort ical neurons inhibited neurite outgrowth. Furthermore, expression of active Abl resulted in lengthening of neurites. The data provide evidence for a C ables-mediated interplay between the Cdk5 and c-Abl signaling pathways in t he developing nervous system.