title: DOCK7 is a critical regulator of the RAGE-Cdc42 signaling axis that             induces formation of dendritic pseudopodia in human cancer cells.
abstract: Cellular migration is a fundamental process linked to cancer metastasis.             Growing evidence indicates that the receptor for advanced glycation end products             (RAGE) plays a pivotal role in this process. With regard to downstream signal             transducers of RAGE, diaphanous-1 and activated small guanine nucleotide triphosphatases,             Rac1 and Cdc42, have been identified. To obtain precise insight into the direct             downstream signaling mechanism of RAGE, we screened for proteins interacting with             the cytoplasmic domain of RAGE employing an immunoprecipitation-liquid chromatography             coupled with an electrospray tandem mass spectrometry system. In the present study,             we found that the cytoplasmic domain of RAGE interacted with an atypical DOCK180-related             guanine nucleotide exchange factor, dedicator of cytokinesis protein 7 (DOCK7).             DOCK7 bound to the RAGE cytoplasmic domain and transduced a signal to Cdc42, resulting             in the formation of abundant highly branched filopodia-like protrusions, dendritic             pseudopodia. Blocking of the function of DOCK7 greatly abrogated the formation             of dendritic pseudopodia and suppressed cellular migration. These results indicate             that DOCK7 functions as an essential and downstream regulator of RAGE-mediated             cellular migration through the formation of dendritic pseudopodia.
authors.affiliation: Department of Cell Biology, Okayama University Graduate School                     of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama 700-8558,                     Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Murata
authors.forename: Endy Widya
authors.initials: EW
authors.lastname: Putranto
authors.forename: Ken
authors.initials: K
authors.lastname: Kataoka
authors.forename: Akira
authors.initials: A
authors.lastname: Motoyama
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hibino
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Inoue
authors.forename: Masakiyo
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: Nam-Ho
authors.initials: NH
authors.lastname: Huh
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D003712:Dendrites / Q000378:metabolism*; D004789:Enzyme Activation; D020690:GTPase-Activating Proteins / Q000502:physiology*; D005909:Glioblastoma; D020662:Guanine Nucleotide Exchange Factors; D057809:HEK293 Cells; D006801:Humans; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011554:Pseudopodia / Q000378:metabolism*; D000067759:Receptor for Advanced Glycation End Products / Q000737:chemistry / Q000378:metabolism*; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism; D015398:Signal Transduction; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*
chemical_list: C514577:DOCK7 protein, human; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D000067759:Receptor for Advanced Glycation End Products; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; D020764:cdc42 GTP-Binding Protein