Fig. 9. Model for the role of β-catenin tyrosine phosphorylation in axon growth and branching. Adhesion complexes are assembled at the plasma membrane of the cell body, axon and growth cone. β-catenin residue Y654 is found at the region that binds to N-cadherin, whereas β-catenin Y142 is in the -catenin-binding region (Aberle et al., 1996; Lilien and Balsamo, 2005). -catenin also binds to actin (Drees et al., 2005; Yamada et al., 2005). Trk and Met associate with a pool of β-catenin that is bound to N-cadherin and -catenin. β-catenin phosphorylation by HGF-Met signalling at β-catenin Y142 targets β-catenin to the nucleus, where it activates TCF4-mediated transcription to increase axon growth and branching. The detachment of Y142-P β-catenin from the adhesion complex might imply dynamic regulation of Y654 phosphorylation, perhaps by Src-family tyrosine kinases (Roura et al., 1999), and its dephosphorylation before nuclear translocation of Y142-P β-catenin (according to the lack of nuclear immunostaining for Y654-P β-catenin). β-catenin phosphorylation by NT-Trk signalling at Y654 detaches β-catenin from N-cadherin (Bamji et al., 2006; Huber and Weis, 2001; Lilien and Balsamo, 2005; Roura et al., 1999), and Y654-P β-catenin associates with actin and microtubules at the growth cone, possibly regulating the cytoskeleton to promote axon growth and branching. Note that, whereas we demonstrate that β-catenin–-catenin dissociates upon phosphorylation of β-catenin Y142, the depicted β-catenin dissociation from N-cadherin upon Y654 phosphorylation is based on the references above. For simplicity, Met has been located at the cell body and Trk at the growth-cone plasma membrane. N, N-cadherin; β, β-catenin; , -catenin; ––, F-actin; ^....., microtubules.