Neurobiology Linking Cdk5 and Abl With Cables

Cyclin-dependent kinase 5 (Cdk5) is a serine-threonine kinase that regulates neural development, particularly normal neuronal migration, but the paucity of known interacting molecules has made it difficult to understand molecular interactions that regulate this function. Zukerberg et al. have identified a protein that interacts with both Cdk5 and the tyrosine kinase Abl, called Cables. Cables associated with both kinases in a ternary complex in transfected cells, and all three proteins colocalized to axonal growth cones of cultured cortical neurons. Cables is phosphorylated by Ckd5 and by Abl, and phosphorylation of Cdk5 by Abl increased Cdk5 activity. Because Abl does not directly associate with Cdk5, Cables likely facilitates their interaction by acting as an adaptor protein. Expression of an antisense Cables construct in cortical neurons inhibited neurite outgrowth. The authors propose that phosphorylation of Cdk5 by Abl may cause dissociation of the Cdk5-Cables-Abl complex and thus allow Cdk5 to interact with its regulatory subunit p35 and to phosphorylate substrates that are involved in neurite outgrowth.

Zukerberg, L.R., Patrick, G.N., Nikolic, M., Humbert, S., Wu, C.-L., Lanier, L.M., Gertler, F.B., Vidal, M., Van Etten, R.A., and Tsai, L.-H. (2000) Cables links Cdk5 and c-Abl and facilitates Cdk5 tyrosine phosphorylation, kinase upregulation, and neurite outgrowth. Neuron 26: 633-646. [Online Journal]

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