Ankyrin repeat domain 28 (ANKRD28), a novel binding partner of DOCK180, promotes cell migration by regulating focal adhesion formation

作者: Mitsuhiro Tachibana , Etsuko Kiyokawa , Shigeo Hara , Shun-ichiro Iemura , Tohru Natsume

DOI: 10.1016/J.YEXCR.2008.12.005

关键词: Ankyrin repeatCell biologySH3 domainFocal adhesionCrk-Associated Substrate ProteinPaxillinSignal transducing adaptor proteinBiologyAdapter molecule crkDock180

摘要: DOCK180 is a guanine exchange factor of Rac1 originally identified as protein bound to an SH3 domain the Crk adaptor protein. induces tyrosine phosphorylation p130(Cas), and recruits Crk-p130(Cas) complex focal adhesions. To understand role in cell adhesion migration, we searched for DOCK180-binding proteins with nano-LC/MS/MS system, ANKRD28, that contains twenty-six ankyrin repeats. Knockdown ANKRD28 by RNA interference reduced velocity migration HeLa cells, suggesting this plays physiologic DOCK180-Rac1 signaling pathway. Furthermore, knockdown was found alter distribution such Crk, paxillin, p130(Cas). On other hand, expression induced hyper-phosphorylation impaired detachment membrane during migration. Consequently, cells expressing exhibited multiple long cellular processes. associated SH3-dependent manner competed ELMO, another DOCK180. In striking contrast overexpression ELMO extensive lamellipodial protrusion around entire circumference. These data suggest specifies localization activity

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