Cables links Robo-bound Abl kinase to N-cadherin-bound β-catenin to mediate Slit-induced modulation of adhesion and transcription

J Rhee, T Buchan, L Zukerberg, J Lilien… - Nature cell biology, 2007 - nature.com
J Rhee, T Buchan, L Zukerberg, J Lilien, J Balsamo
Nature cell biology, 2007nature.com
Binding of the secreted axon guidance cue Slit to its Robo receptor results in inactivation of
the neural, calcium-dependent cell–cell adhesion molecule N-cadherin, providing a rapid
epigenetic mechanism for integrating guidance and adhesion information. This requires the
formation of a multimolecular complex containing Robo, Abl tyrosine kinase and N-cadherin.
Here we show that on binding of Slit to Robo, the adaptor protein Cables is recruited to
Robo-associated Abl and forms a multimeric complex by binding directly to N-cadherin …
Abstract
Binding of the secreted axon guidance cue Slit to its Robo receptor results in inactivation of the neural, calcium-dependent cell–cell adhesion molecule N-cadherin, providing a rapid epigenetic mechanism for integrating guidance and adhesion information. This requires the formation of a multimolecular complex containing Robo, Abl tyrosine kinase and N-cadherin. Here we show that on binding of Slit to Robo, the adaptor protein Cables is recruited to Robo-associated Abl and forms a multimeric complex by binding directly to N-cadherin-associated β-catenin. Complex formation results in Abl-mediated phosphorylation of β-catenin on tyrosine 489, leading to a decrease in its affinity for N-cadherin, loss of N-cadherin function, and targeting of phospho-Y489-β-catenin to the nucleus. Nuclear β-catenin combines with the transcription factor Tcf/Lef and activates transcription. Thus, Slit-induced formation of the Robo–N-cadherin complex results in a rapid loss of cadherin-mediated adhesion and has more lasting effects on gene transcription.
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