title: Arf GTPase-activating protein AGAP2 regulates focal adhesion kinase activity and focal adhesion remodeling.
abstract: Focal adhesions are specialized sites of cell attachment to the extracellular matrix where integrin receptors link extracellular matrix to the actin cytoskeleton, and they are constantly remodeled during cell migration. Focal adhesion kinase (FAK) is an important regulator of focal adhesion remodeling. AGAP2 is an Arf GTPase-activating protein that regulates endosomal trafficking and is overexpressed in different human cancers. Here we examined the regulation of the FAK activity and the focal adhesion remodeling by AGAP2. Our results show that FAK binds the pleckstrin homology domain of AGAP2, and the binding is independent of FAK activation following epidermal growth factor receptor stimulation. Overexpression of AGAP2 augments the activity of FAK, and concordantly, the knockdown of AGAP2 expression with RNA interference attenuates the FAK activity stimulated by epidermal growth factor or platelet-derived growth factor receptors. AGAP2 is localized to the focal adhesions, and its overexpression results in dissolution of the focal adhesions, whereas knockdown of its expression stabilizes them. The AGAP2-induced dissolution of the focal adhesions is independent of its GTPase-activating protein activity but may involve its N-terminal G protein-like domain. Our results indicate that AGAP2 regulates the FAK activity and the focal adhesion disassembly during cell migration.
authors.affiliation: Department of Pathology, Medical College of Georgia, Augusta, Georgia 30912.
authors.forename: Yunjuan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Medical College of Georgia, Augusta, Georgia 30912.
authors.forename: Yuanjun
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pathology, Medical College of Georgia, Augusta, Georgia 30912.
authors.forename: Jae I
authors.initials: JI
authors.lastname: Kim
authors.affiliation: Department of Pathology, Medical College of Georgia, Augusta, Georgia 30912.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pathology, Medical College of Georgia, Augusta, Georgia 30912.
authors.forename: Yehia
authors.initials: Y
authors.lastname: Daaka
authors.affiliation: Department of Pathology, Medical College of Georgia, Augusta, Georgia 30912. Electronic address: znie@mcg.edu.
authors.forename: Zhongzhen
authors.initials: Z
authors.lastname: Nie