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Publication : EphB2 receptor forward signaling controls cortical growth cone collapse via Nck and Pak.

First Author  Srivastava N Year  2013
Journal  Mol Cell Neurosci Volume  52
Pages  106-16 PubMed ID  23147113
Mgi Jnum  J:203654 Mgi Id  MGI:5528433
Doi  10.1016/j.mcn.2012.11.003 Citation  Srivastava N, et al. (2013) EphB2 receptor forward signaling controls cortical growth cone collapse via Nck and Pak. Mol Cell Neurosci 52:106-16
abstractText  EphB receptors and their ephrinB ligands transduce bidirectional signals that mediate contact-dependent axon guidance primarily by promoting growth cone repulsion. However, how EphB receptor-mediated forward signaling induces axonal repulsion remains poorly understood. Here, we identify Nck and Pak proteins as essential forward signaling components of EphB2-dependent growth cone collapse in cortical neurons. We show that kinase-active EphB2 binds to Pak and promotes growth cone repulsion via Pak kinase activity, Pak-Nck binding, RhoA signaling and endocytosis. However, Pak's function in this context appears to be independent of Rac/Cdc42-GTP, consistent with the absence of Rac-GTP production after ephrinB treatment of cortical neurons. Taken together, our findings suggest that ephrinB-activated EphB2 receptors recruit a novel Nck/Pak signaling complex to mediate repulsive cortical growth cone guidance, which may be relevant for EphB forward signaling-dependent axon guidance in vivo.
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