title: IQGAP1 is a novel CXCR2-interacting protein and essential component of the "chemosynapse".
abstract: BACKGROUND
  Chemotaxis is essential for a number of physiological processes including leukocyte recruitment. Chemokines initiate intracellular signaling pathways necessary for chemotaxis through binding seven transmembrane G protein-couple receptors. Little is known about the proteins that interact with the intracellular domains of chemokine receptors to initiate cellular signaling upon ligand binding. CXCR2 is a major chemokine receptor expressed on several cell types, including endothelial cells and neutrophils. We hypothesize that multiple proteins interact with the intracellular domains of CXCR2 upon ligand stimulation and these interactions comprise a "chemosynapse", and play important roles in transducing CXCR2 mediated signaling processes.
  
  
  RESULTS
  In an effort to define the complex of proteins that assemble upon CXCR2 activation to relay signals from activated chemokine receptors, a proteomics approach was employed to identify proteins that co-associate with CXCR2 with or without ligand stimulation. The components of the CXCR2 "chemosynapse" are involved in processes ranging from intracellular trafficking to cytoskeletal modification. IQ motif containing GTPase activating protein 1 (IQGAP1) was among the novel proteins identified to interact directly with CXCR2. Herein, we demonstrate that CXCR2 co-localizes with IQGAP1 at the leading edge of polarized human neutrophils and CXCR2 expressing differentiated HL-60 cells. Moreover, amino acids 1-160 of IQGAP1 directly interact with the carboxyl-terminal domain of CXCR2 and stimulation with CXCL8 enhances IQGAP1 association with Cdc42.
  
  
  CONCLUSIONS
  Our studies indicate that IQGAP1 is a novel essential component of the CXCR2 "chemosynapse".
authors.affiliation: Department of Veterans Affairs, Nashville, Tennessee, United States of America.
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Neel
authors.forename: Jiqing
authors.initials: J
authors.lastname: Sai
authors.forename: Amy-Joan L
authors.initials: AJ
authors.lastname: Ham
authors.forename: Tammy
authors.initials: T
authors.lastname: Sobolik-Delmaire
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Mernaugh
authors.forename: Ann
authors.initials: A
authors.lastname: Richmond
mesh_terms: D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D002853:Chromatography, Liquid; D057809:HEK293 Cells; D018922:HL-60 Cells; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects / Q000378:metabolism*; D016209:Interleukin-8 / Q000494:pharmacology; D013058:Mass Spectrometry; D011485:Protein Binding / Q000187:drug effects; D040901:Proteomics; D023063:Receptors, Interleukin-8B / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: C101203:IQ motif containing GTPase activating protein 1; D016209:Interleukin-8; D023063:Receptors, Interleukin-8B; D020703:ras GTPase-Activating Proteins; D020764:cdc42 GTP-Binding Protein