Cables, a 568 amino-acid protein, links Abl to cyclin-dependent kinase 5 (Cdk5). Cables bound to Cdk5 functions as a substrate for phosphorylation by the Cdk5/p35 kinase. Cables contains an area of weak homology to cyclin A and cyclin C. In addition to its C-terminal Cdk5 binding domain, Cables also has six potential SH3 binding motifs (PXXP) clustered around the amino terminus, two of which are similar to motifs known to bind the Abl SH3 domain. Cables forms a trimolecular complexwith Cdk5 and Abl in vivo. All three proteins colocalize within cortical axons, particularly in their growth cones. Cables and Abl may function as adaptor or scaffolding proteins to bind to Cdk5 and control its subcellular location in the neuron.