N-WASP is a member of the WASP family of proteins that regulate actin cytoskeleton remodeling. FAK is a cytoplasmic tyrosine kinase implicated in integrin signaling during cell migration. Here we identify a direct interaction between N-WASP and FAK and show that N-WASP is phosphorylated by FAK at a conserved iyo tyrosine residue, Tyr256. We found that phosphorylation of Tyr256 affected N-WASP nuclear localization, suggesting that phosphorylation of N-WASP by FAK may regulate its activity in vivo by altering its subcellular localization. We also showed that the nuclear localization of N-WASP is dependent on its being in the open conformation either after its activation by Cdc42 or the truncation of the C-terminal VCA domain. Phosphorylation of Tyr256 of N-WASP could reduce its interaction with nuclear importin NPI-1, which might be responsible for its decreased nuclear localization. Lastly, we show that phosphorylation of Tyr 256 plays an important role in promoting cell migration. Together, these results suggest a novel regulatory mechanism of N-WASP by tyrosine phosphorylation and subcellular localization and its potential role in the regulation of cell migration.
CITATION STYLE
Wu, X., Suetsugu, S., Cooper, L. A., Takenawa, T., & Guan, J. L. (2004). Focal Adhesion Kinase Regulation of N-WASP Subcellular Localization and Function. Journal of Biological Chemistry, 279(10), 9565–9576. https://doi.org/10.1074/jbc.M310739200
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