Phosphatidic Acid-dependent Recruitment and Function of the Rac Activator DOCK1 during Dorsal Ruffle Formation

Sanematsu, Fumiyuki; Nishikimi, Akihiko; Watanabe, Masayoshi; Hongu, Tsunaki; Tanaka, Yoshihiko; Kanaho, Yasunori; Côté, Jean; Fukui, Yoshihiro

doi:10.1074/jbc.m112.410423

Cited by 46 publications

(34 citation statements)

References 49 publications

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“…Pdgf treatment of fibroblasts promotes a rapid DHR-1-dependent and PIP 3 -dependent recruitment of both Dock1 and Dock5 at the membrane, resulting in the activation of Rac1 to form peripheral ruffles. As in neutrophils, PA production lags behind that of PIP 3 and acts to focus the localization of Dock1 (but not Dock5, as it lacks a PBR) at the membrane to generate the characteristic Pdgf-induced dorsal ruffles (Sanematsu et al 2013). These data highlight the importance of localizing individual Dock family members for specific biological functions.…”

Section: Lipids and Scaffolds: Spatiotemporal Activation Of Docksmentioning

confidence: 86%

“…A polybasic region (PBR) (see Fig. 1) in Dock1 and Dock2 was initially thought to bind PIP 3 , but more recent data suggest that it binds the signaling lipid phosphatidic acid (PA) (Kobayashi et al 2001;Nishikimi et al 2009;Sanematsu et al 2013). Insight into the biological role of this second lipid-binding activity Ó 2014 Laurin and Cô té This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml).…”

Section: Lipids and Scaffolds: Spatiotemporal Activation Of Docksmentioning

confidence: 99%

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Insights into the biological functions of Dock family guanine nucleotide exchange factors

2014

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Rho GTPases play key regulatory roles in many aspects of embryonic development, regulating processes such as differentiation, proliferation, morphogenesis, and migration. Two families of guanine nucleotide exchange factors (GEFs) found in metazoans, Dbl and Dock, are responsible for the spatiotemporal activation of Rac and Cdc42 proteins and their downstream signaling pathways. This review focuses on the emerging roles of the mammalian DOCK family in development and disease. We also discuss, when possible, how recent discoveries concerning the biological functions of these GEFs might be exploited for the development of novel therapeutic strategies.

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Section: Lipids and Scaffolds: Spatiotemporal Activation Of Docksmentioning

confidence: 86%

Section: Lipids and Scaffolds: Spatiotemporal Activation Of Docksmentioning

confidence: 99%

Insights into the biological functions of Dock family guanine nucleotide exchange factors

2014

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“…For example, DOCK1 and DOCK5, as well as DOCK2, belong to the DOCK-A subfamily and act as Rac-specific GEFs (10,19). DOCK1 and DOCK5 are widely expressed in various tissues and regulate multiple cellular functions, including myoblast fusion, bone resorption, and migration (20)(21)(22); however, their roles in the immune system and immune responses are poorly understood. We found that neutrophils also express DOCK5, but not DOCK1.…”

mentioning

confidence: 99%

DOCK2 and DOCK5 Act Additively in Neutrophils To Regulate Chemotaxis, Superoxide Production, and Extracellular Trap Formation

Watanabe

Terasawa

Miyano

et al. 2014

The Journal of Immunology

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Neutrophils are highly motile leukocytes that play important roles in the innate immune response to invading pathogens. Neutrophils rapidly migrate to the site of infections and kill pathogens by producing reactive oxygen species (ROS). Neutrophil chemotaxis and ROS production require activation of Rac small GTPase. DOCK2, an atypical guanine nucleotide exchange factor (GEF), is one of the major regulators of Rac in neutrophils. However, because DOCK2 deficiency does not completely abolish fMLF-induced Rac activation, other Rac GEFs may also participate in this process. In this study, we show that DOCK5 acts with DOCK2 in neutrophils to regulate multiple cellular functions. We found that fMLF- and PMA-induced Rac activation were almost completely lost in mouse neutrophils lacking both DOCK2 and DOCK5. Although β2 integrin–mediated adhesion occurred normally even in the absence of DOCK2 and DOCK5, mouse neutrophils lacking DOCK2 and DOCK5 exhibited a severe defect in chemotaxis and ROS production. Similar results were obtained when human neutrophils were treated with CPYPP, a small-molecule inhibitor of these DOCK GEFs. Additionally, we found that DOCK2 and DOCK5 regulate formation of neutrophil extracellular traps (NETs). Because NETs are involved in vascular inflammation and autoimmune responses, DOCK2 and DOCK5 would be a therapeutic target for controlling NET-mediated inflammatory disorders.

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“…In PDGF-induced dorsal ruffle formation pathway in mammalian cells, Abl signals to activate Rac [28, 35, 53–56]. This activation might involve DOCK180 since the complex of Crk/DOCK180 has been shown to control Rac activation during dorsal ruffle formation [57] (Fig. 4F).…”

Section: Discussionmentioning

confidence: 99%

G-Protein Gα13 Functions with Abl Kinase to Regulate Actin Cytoskeletal Reorganization

Wang

Xing

et al. 2017

Journal of Molecular Biology

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Heterotrimeric G-proteins are essential cellular signal transducers. One of the G-proteins, Gα13, is critical for actin cytoskeletal reorganization, cell migration, cell proliferation and apoptosis. Previously we have shown that Gα13 is essential for both G protein-coupled receptor (GPCR) and receptor tyrosine kinase (RTK)-induced actin cytoskeletal reorganization such as dynamic dorsal ruffle turnover and cell migration. However, the mechanism by which Gα13 signals to actin cytoskeletal reorganization is not completely understood. Here we show that Gα13 directly interacts with Abl tyrosine kinase which is a critical regulator of actin cytoskeleton. This interaction is critical for Gα13-induced dorsal ruffle turnover, endothelial cell remodeling, and cell migration. Our data uncover a new molecular signaling pathway by which Gα13 controls actin cytoskeletal reorganization.

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Phosphatidic Acid-dependent Recruitment and Function of the Rac Activator DOCK1 during Dorsal Ruffle Formation

Cited by 46 publications

References 49 publications

Insights into the biological functions of Dock family guanine nucleotide exchange factors

Insights into the biological functions of Dock family guanine nucleotide exchange factors

DOCK2 and DOCK5 Act Additively in Neutrophils To Regulate Chemotaxis, Superoxide Production, and Extracellular Trap Formation

G-Protein Gα13 Functions with Abl Kinase to Regulate Actin Cytoskeletal Reorganization

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