Article abstract
Nature Cell Biology 9, 883 - 892 (2007)
Published online: 8 July 2007 | doi:10.1038/ncb1614
Cables links Robo-bound Abl kinase to N-cadherin-bound 
-catenin to mediate Slit-induced modulation of adhesion and transcription
Jinseol Rhee1,3, Tim Buchan1, Lawrence Zukerberg2, Jack Lilien1 & Janne Balsamo1
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 
-catenin. Complex formation results in Abl-mediated phosphorylation of -catenin on tyrosine 489, leading to a decrease in its affinity for N-cadherin, loss of N-cadherin function, and targeting of phospho-Y489--catenin to the nucleus. Nuclear -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.
- Department of Biological Sciences, The University of Iowa, Iowa City, Iowa 52242-1324, USA.
- Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts 02115, USA.
- Current address: Howard Hughes Medical Institute, Department of Physiology, University of California, 1550 Fourth Street, San Francisco, California 94143-2611, USA.
Correspondence to: Jack Lilien1 e-mail: jack-lilien@uiowa.edu
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