更新于：2024-11-01

Kainate受体 x GluK5

更新于：2024-11-01

基本信息

关联

项与 Kainate受体 x GluK5 相关的药物

LY-466195

靶点

GluK5 x Kainate受体

作用机制

GluK5 antagonists [+1]

在研机构

Eli Lilly & Co. [+1]

原研机构

Eli Lilly & Co.

在研适应症

偏头痛

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 Kainate受体 x GluK5 相关的临床结果

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100 项与 Kainate受体 x GluK5 相关的转化医学

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0 项与 Kainate受体 x GluK5 相关的专利（医药）

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123

项与 Kainate受体 x GluK5 相关的文献（医药）

2023-07-01·Cell biology international

GRIK5 stimulates colon cancer growth and metastasis through cAMP/PKA/CADM3 signaling.

Article

作者: Xie, Zhengyong ; Chen, Yuhong ; Li, Zehang ; Ding, Hongliang ; Ke, Yongli ; Chen, Guijin ; Cheng, Liyang ; Chen, Junyong ; Wang, Changzheng ; Lei, Deqiao

Glutamate receptor, ionotropic, kainate 5 (GRIK5) is a member of glutamate receptors participating, and the kainate receptor family has been proved to regulate cell proliferation and transformation. Our study aimed at exploring the role of GRIK5 in colon tumor progression. Three hundred and ninety eight colon cancer patients in The Cancer Genome Atlas Program (TCGA) data set and 26 clinical colon cancer patients were included for GRIK5 expression and prognosis analysis. GRIK5 overexpressed HCT116 and CT26 cell lines were established for cell proliferation and Transwell assay. Western blot analysis and immunostaining assay was conducted to evaluate the activation of activation of cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cell adhesion molecular 3 (CADM3) signaling in cell lines and tumor tissues. Subcutaneous CT26-bearing mice model was established to examine GRIK5-induced tumor growth and metastasis in vivo. Our study identified GRIK5 to be upregulated in patients with colon cancer, and higher GRIK5 levels correlated with the poor overall survival in patients. In vitro, GRIK5 overexpression markedly enhanced the proliferative properties and aggressive behaviors of colon cancer cells. Mechanistically, GRIK5 induced the activation of cAMP/PKA signaling, proceeded with augmented CADM3 expression, eventually resulting in sustained tumor growth. GRIK5 was a crucial scaffold in enabling colon cancer growth and metastasis, which offered a promising target for therapeutic manipulation of colon cancer.

2022-01-01·Subcellular Biochemistry

Structure, Function, and Regulation of the Kainate Receptor

Review

作者: Kumar, Janesh ; Yadav, Juhi ; Dhingra, Surbhi

Neural communication and modulation are complex processes. Ionotropic glutamate receptors (iGluRs) significantly contribute to mediating the fast-excitatory branch of neurotransmission in the mammalian brain. Kainate receptors (KARs), a subfamily of the iGluRs, act as modulators of the neuronal circuitry by playing important roles at both the post- and presynaptic sites of specific neurons. The functional tetrameric receptors are formed by two different gene families, low agonist affinity (GluK1-GluK3) and high agonist affinity (GluK4-GluK5) subunits. These receptors garnered attention in the past three decades, and since then, much work has been done to understand their localization, interactome, physiological functions, and regulation. Cloning of the receptor subunits (GluK1-GluK5) in the early 1990s led to recombinant expression of kainate receptors in heterologous systems. This facilitated understanding of the functional differences between subunit combinations, splice variants, trafficking, and drug discovery. Structural studies of individual domains and recent full-length homomeric and heteromeric kainate receptors have revealed unique functional mechanisms, which have answered several long-standing questions in the field of kainate receptor biology. In this chapter, we review the current understanding of kainate receptors and associated disorders.

2021-06-01·Neuropharmacology2区 · 医学

Structural biology of kainate receptors

2区 · 医学

Review

作者: Mayer, Mark L

This review summarizes structural studies on kainate receptors that explain unique functional properties of this receptor family. A large number of structures have been solved for ligand binding domain dimer assemblies, giving insight into the subtype selective pharmacology of agonists, antagonists, and allosteric modulators. Structures and biochemical studies on the amino terminal domain reveal mechanisms that play a key role in assembly of heteromeric receptors. Surprisingly, structures of full length homomeric GluK2, GluK3 and heteromeric GluK2/GluK5, receptors reveal a novel structure for the desensitized state that is strikingly different from that for AMPA receptors.