RRC ID 44208
著者 Yamamoto K, Murata H, Putranto EW, Kataoka K, Motoyama A, Hibino T, Inoue Y, Sakaguchi M, Huh NH.
タイトル DOCK7 is a critical regulator of the RAGE-Cdc42 signaling axis that induces formation of dendritic pseudopodia in human cancer cells.
ジャーナル Oncol Rep
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.
巻・号 29(3)
ページ 1073-9
公開日 2013-3-1
DOI 10.3892/or.2012.2191
PMID 23254359
MeSH Cell Line, Tumor Cell Movement Dendrites / metabolism* Enzyme Activation GTPase-Activating Proteins / physiology* Glioblastoma Guanine Nucleotide Exchange Factors HEK293 Cells Humans Protein Binding Protein Interaction Domains and Motifs Pseudopodia / metabolism* Receptor for Advanced Glycation End Products / chemistry Receptor for Advanced Glycation End Products / metabolism* S100 Calcium Binding Protein beta Subunit / metabolism Signal Transduction cdc42 GTP-Binding Protein / metabolism*
IF 3.417
引用数 17
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 293T(RCB2202)