title: Direct Functional Interaction of the Kinesin-13 Family Member Kinesin-like Protein 2A (Kif2A) and Arf GAP with GTP-binding Protein-like, Ankyrin Repeats and PH Domains1 (AGAP1).
abstract: The molecular basis for control of the cytoskeleton by the Arf GTPase-activating protein AGAP1 has not been characterized. AGAP1 is composed of G-protein-like (GLD), pleckstrin homology (PH), Arf GAP, and ankyrin repeat domains. Kif2A was identified in screens for proteins that bind to AGAP1. The GLD and PH domains of AGAP1 bound the motor domain of Kif2A. Kif2A increased GAP activity of AGAP1, and a protein composed of the GLD and PH domains of AGAP1 increased ATPase activity of Kif2A. Knockdown (KD) of Kif2A or AGAP1 slowed cell migration and accelerated cell spreading. The effect of Kif2A KD on spreading could be rescued by expression of Kif2A-GFP or FLAG-AGAP1, but not by Kif2C-GFP. The effect of AGAP1 KD could be rescued by FLAG-AGAP1, but not by an AGAP1 mutant that did not bind Kif2A efficiently, ArfGAP1-HA or Kif2A-GFP. Taken together, the results support the hypothesis that the Kif2A·AGAP1 complex contributes to control of cytoskeleton remodeling involved in cell movement.
authors.affiliation: From the Laboratory of Cellular and Molecular Biology and.
authors.forename: Ruibai
authors.initials: R
authors.lastname: Luo
authors.affiliation: From the Laboratory of Cellular and Molecular Biology and.|the Department of Biology, Grinnell College, Grinnell, Iowa 50112, and.
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Chen
authors.affiliation: the Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, Washington 98195.
authors.forename: Michael
authors.initials: M
authors.lastname: Wagenbach
authors.affiliation: From the Laboratory of Cellular and Molecular Biology and.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Jian
authors.affiliation: Laboratory of Cell Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Lisa
authors.initials: L
authors.lastname: Jenkins
authors.affiliation: the Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, Washington 98195.
authors.forename: Linda
authors.initials: L
authors.lastname: Wordeman
authors.affiliation: From the Laboratory of Cellular and Molecular Biology and randazzp@mail.nih.gov.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Randazzo
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D020690:GTPase-Activating Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C470574:AGAP1 protein, human; D020690:GTPase-Activating Proteins; C509805:KIF2A protein, human; D016547:Kinesins
keywords: ADP ribosylation factor (ARF); AGAP1; Arf GTPase-activating protein; GTPase activating protein (GAP); Kif2A; PH domain; cell biology; enzyme; kinesin; kinesin-13; protein complex; small GTPase