NCK1 or NCK2, orthologues of Drosophila Dock, bound to ROBO1 receptor, recruits PAK to specific sites at the growth cone membrane, where PAK, activated by RAC1, regulates the recycling and retrograde flow of actin filaments. In mammals, there are six PAK isoforms (PAK1-6) and PAK binds to the 2nd SH3 domain of NCK with its proline rich PxxP motif (Galisteo et al. 1996, Fan et al. 2003). PAK autophosphorylation triggered by RAC1/CDC42 activation disrupts PAK interaction with NCK proteins (Zhao et al. 2000).
Lim, L, Manser, E, Zhao, ZS
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