更新于：2024-11-01

DOCK5

更新于：2024-11-01

基本信息

别名

dedicator of cytokinesis 5、Dedicator of cytokinesis protein 5、DOCK5

+ [1]

简介

Guanine nucleotide exchange factor (GEF) for Rho and Rac. GEF proteins activate small GTPases by exchanging bound GDP for free GTP (By similarity). Along with DOCK1, mediates CRK/CRKL regulation of epithelial and endothelial cell spreading and migration on type IV collagen (PubMed:19004829).

关联

项与 DOCK5 相关的药物

Alprazolam

阿普唑仑

靶点

DOCK5 x GABAA receptor

作用机制

DOCK5抑制剂 [+1]

在研机构

UCB Biopharma SRL [+7]

原研机构

Takeda Pharmaceutical Co., Ltd. [+1]

在研适应症

紧张症 [+6]

非在研适应症

药物滥用 [+2]

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期1981-10-16

111

项与 DOCK5 相关的临床试验

IRCT20240506061669N1 / Recruiting临床3期IIT

Comparing the effect of Alprazolam (single dose) and Clonidine on improving the patient's stability under General Anesthesia

开始日期2024-05-21

申办/合作机构

Islamic Azad University

CTR20241558 / CompletedN/A

阿普唑仑片在空腹及餐后条件下的人体生物等效性试验

本研究考察健康受试者在空腹及餐后条件下，单次口服由湖南洞庭药业股份有限公司生产的阿普唑仑片（受试制剂，规格：0.4 mg）或由ヴィアトリス製薬株式会社（Viatoris制药株式会社）持证的阿普唑仑片（参比制剂，商品名：Solanax®，规格：0.4 mg）的药动学特征，评价两制剂的生物等效性及安全性，该受试制剂一致性评价提供依据。

开始日期2024-05-14

申办/合作机构

湖南洞庭药业股份有限公司

NCT06293638 / RecruitingN/AIIT

Functional Brain Network Changes in Patients Undergoing Deep Brain Stimulation for Essential Tremor

The purpose of this study is to collect electrophysiological data related to functional brain network changes in patients undergoing deep brain stimulation for the treatment of essential tremor. Participants will be asked to remain seated with their head inside of a Magnetoencephalography (MEG) recording system as resting-state and task-related data are acquired. Spontaneous electrophysiological activity will be recorded in both the eyes open and eyes closed conditions with the participant seated comfortably. These recordings will be repeated in the DBS OFF and DBS ON states, with the ON state involving specific settings identified as optimal, sub-optimal, or ineffective at achieving tremor control. They will also be repeated following the optional administration non-DBS tremor mitigation techniques, which may include one or more of 1) cooling the limb, 2) oral administration of alprazolam, 3) oral consumption of ethanol (alcohol), or 4) peripheral nerve stimulation.

开始日期2024-03-25

申办/合作机构-

100 项与 DOCK5 相关的临床结果

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100 项与 DOCK5 相关的转化医学

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0 项与 DOCK5 相关的专利（医药）

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项与 DOCK5 相关的文献（医药）

2024-10-01·Advanced Science

Liraglutide Promotes Diabetic Wound Healing via Myo1c/Dock5

Article

作者: Zhu, Jiaran ; Wang, Yuren ; Zheng, Hongting ; Li, Hongwei ; Tong, Qiang ; Kang, Changjiang ; He, Qingshan ; Zhang, Linlin ; Zheng, Yi ; Zhang, Qian ; Zhang, Chunlin ; Xiong, Xin ; Qu, Hua ; Wang, Min

AbstractNon‐healing diabetic wounds and ulcer complications, with persistent cell dysfunction and obstructed cellular processes, are leading causes of disability and death in patients with diabetes. Currently, there is a lack of guideline‐recommended hypoglycemic drugs in clinical practice, likely due to limited research and unclear mechanisms. In this study, it is demonstrated that liraglutide significantly accelerates wound closure in diabetic mouse models (db/db mice and streptozotocin‐induced mice) by improving re‐epithelialization, collagen deposition, and extracellular matrix remodeling, and enhancing the proliferation, migration, and adhesion functions of keratinocytes. However, these effects of improved healing by liraglutide are abrogated in dedicator of cytokinesis 5 (Dock5) keratinocyte‐specific knockout mice. Mechanistically, liraglutide induces cellular function through stabilization of unconventional myosin 1c (Myo1c). Liraglutide directly binds to Myo1c at arginine 93, enhancing the Myo1c/Dock5 interaction by targeting Dock5 promoter and thus promoting the proliferation, migration, and adhesion of keratinocytes. Therefore, this study provides insights into liraglutide biology and suggests it may be an effective treatment for diabetic patients with wound‐healing pathologies.

2024-09-01·Hepatology Research

Genomic analysis of an aggressive hepatic leiomyosarcoma case following treatment for hepatocellular carcinoma

Article

作者: Numata, Yuto ; Ishigami, Keisuike ; Hirano, Takehiro ; Murota, Ayako ; Akutsu, Noriyuki ; Nakase, Hiroshi ; Nakamura, Tomoya ; Idogawa, Masashi ; Sasaki, Shigeru ; Wagatsuma, Kohei ; Masaki, Yoshiharu ; Kawakami, Yujiro ; Numata, Yasunao

AbstractA 70‐year‐old man undergoing treatment for immunoglobulin G4‐related disease developed a liver mass on computed tomography during routine imaging examination. The tumor was located in the hepatic S1/4 region, was 38 mm in size, and showed arterial enhancement on dynamic contrast‐enhanced computed tomography. We performed a liver biopsy and diagnosed moderately differentiated hepatocellular carcinoma. The patient underwent proton beam therapy. The tumor remained unchanged but enlarged after 4 years. The patient was diagnosed with hepatocellular carcinoma recurrence and received hepatic arterial chemoembolization. However, 1 year later, the patient developed jaundice, and the liver tumor grew in size. Unfortunately, the patient passed away. Autopsy revealed that the tumor consisted of spindle‐shaped cells exhibiting nuclear atypia and a fission pattern and tested positive for α‐smooth muscle actin and vimentin. No hepatocellular carcinoma components were observed, and the patient was pathologically diagnosed with hepatic leiomyosarcoma. Next‐generation sequencing revealed somatic mutations in CACNA2D4, CTNNB1, DOCK5, IPO8, MTMR1, PABPC5, SEMA6D, and ZFP36L1. Based on the genetic mutation, sarcomatoid hepatocarcinoma was the most likely pathogenesis in this case. This mutation is indicative of the transition from sarcomatoid hepatocarcinoma to hepatic leiomyosarcoma.

2024-07-01·Journal of Biological Chemistry

RhoG facilitates a conformational transition in the guanine nucleotide exchange factor complex DOCK5/ELMO1 to an open state

Article

作者: Nakagawa, Reiko ; Zhang, Kam Y J ; Shirouzu, Mikako ; Yonemochi, Mayumi ; Inoue, Mio ; Kukimoto-Niino, Mutsuko ; Mishima-Tsumagari, Chiemi ; Katsura, Kazushige ; Kaushik, Rahul ; Ishizuka-Katsura, Yoshiko

The dedicator of cytokinesis (DOCK)/engulfment and cell motility (ELMO) complex serves as a guanine nucleotide exchange factor (GEF) for the GTPase Rac. RhoG, another GTPase, activates the ELMO-DOCK-Rac pathway during engulfment and migration. Recent cryo-EM structures of the DOCK2/ELMO1 and DOCK2/ELMO1/Rac1 complexes have identified closed and open conformations that are key to understanding the autoinhibition mechanism. Nevertheless, the structural details of RhoG-mediated activation of the DOCK/ELMO complex remain elusive. Herein, we present cryo-EM structures of DOCK5/ELMO1 alone and in complex with RhoG and Rac1. The DOCK5/ELMO1 structure exhibits a closed conformation similar to that of DOCK2/ELMO1, suggesting a shared regulatory mechanism of the autoinhibitory state across DOCK-A/B subfamilies (DOCK1-5). Conversely, the RhoG/DOCK5/ELMO1/Rac1 complex adopts an open conformation that differs from that of the DOCK2/ELMO1/Rac1 complex, with RhoG binding to both ELMO1 and DOCK5. The alignment of the DOCK5 phosphatidylinositol (3,4,5)-trisphosphate binding site with the RhoG C-terminal lipidation site suggests simultaneous binding of RhoG and DOCK5/ELMO1 to the plasma membrane. Structural comparison of the apo and RhoG-bound states revealed that RhoG facilitates a closed-to-open state conformational change of DOCK5/ELMO1. Biochemical and surface plasmon resonance (SPR) assays confirm that RhoG enhances the Rac GEF activity of DOCK5/ELMO1 and increases its binding affinity for Rac1. Further analysis of structural variability underscored the conformational flexibility of the DOCK5/ELMO1/Rac1 complex core, potentially facilitating the proximity of the DOCK5 GEF domain to the plasma membrane. These findings elucidate the structural mechanism underlying the RhoG-induced allosteric activation and membrane binding of the DOCK/ELMO complex.