Activation of EPHAs leads to phosphorylation of ephexin1 (NGEF) on conserved tyrosine (Y) 179 (Y87 in isoform3) by Src family kinases (SFKs). This phosphorylation preferentially activates NGEF’s GDP/GTP exchange activity specifically towards RHOA but not RAC1 and CDC42, thus switching the substrate preference of NGEF and leading to actin cytoskeletal changes that result in growth cone collapse (Sahin et al. 2005, Knoll and Drescher 2004).
protein tyrosine kinase activity of EFNAs:p-EPHAs:SFKs:NGEF [plasma membrane]
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