Format

Send to

Choose Destination
See comment in PubMed Commons below
Nat Cell Biol. 2007 Aug;9(8):883-92. Epub 2007 Jul 8.

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

Author information

1
Department of Biological Sciences, The University of Iowa, Iowa City, Iowa 52242-1324, USA.

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 beta-catenin. Complex formation results in Abl-mediated phosphorylation of beta-catenin on tyrosine 489, leading to a decrease in its affinity for N-cadherin, loss of N-cadherin function, and targeting of phospho-Y489-beta-catenin to the nucleus. Nuclear beta-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.

PMID:
17618275
DOI:
10.1038/ncb1614
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Support Center