Zinc Finger, FYVE Domain Containing Protein 21 (ZFYVE21)

The FYVE domain of ZF21 was required for its membrane localization. Knockdown of ZF21 in human cell lines via small hairpin RNA increased cell adherence to fibronectin (FN1), collagen I, and vitronectin (VTN), but not poly-L-lysine, and reduced cell motility. Knockdown of ZF21 was associated with enhanced cell surface expression of integrin beta-1 (ITGB1) and increased number of focal adhesions. ZF21 did not affect formation of focal adhesions, but appeared to regulate their disassembly. Protein pull-down analysis showed that ZF21 interacted with the focal adhesion protein FAK (PTK2), and domain analysis revealed that the FYVE domain of ZF21 interacted with the kinase domain FAK.ZF21 dephosphorylated tyr397 of FAK, an event crucial for the induction of focal adhesion disassembly.