The myristoylated alanine-rich C-kinase substrates (MARCKS): A membrane-anchored mediator of the cell function.
The myristoylated alanine-rich C-kinase substrates (MARCKS): A membrane-anchored mediator of the cell function.
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DOI：
10.1016/j.autrev.2021.102942
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发表时间：
2021-11
影响因子：
13.6
通讯作者：
Gershwin, M. Eric
中科院分区：
文献类型：
--
作者：
Chen, Zhilei;Zhang, Weici;Selmi, Carlo;Ridgway, William M.;Leung, Patrick S. C.;Zhang, Fengchun;Gershwin, M. Eric
关键词：
富含肉豆油酰基丙氨酸的c激酶底物（MARCKS）和MARCKS相关蛋白（MARCKSL1）是普遍存在的高度保守的膜相关蛋白，参与肌动蛋白细胞骨架、趋化性、运动性、细胞粘附、吞噬和胞外分泌的结构调节。MARCKS包括一个用于膜结合的n端豆蔻酰基化结构域，一个高度保守的MARCKS同源2 （MH2）结构域和一个效应结构域（即磷酸化位点）。MARCKS可以将磷脂酰肌醇- 4,5 -二磷酸（PIP2）隔离在静止细胞质膜的脂筏上，这一作用被蛋白激酶C （PKC）逆转，最终调节免疫功能。MARCKS主要在先天免疫细胞中表达，促进炎症驱动的细胞迁移和粘附以及肿瘤坏死因子（TNF）等细胞因子的分泌。从临床角度来看，MARCKS在精神分裂症和双相情感障碍患者中过度表达，而MARCKS磷酸化的脑水平与阿尔茨海默病相关。此外，MARCKS与许多类型癌症的发生和进展有关。自身免疫性疾病的数据仅限于类风湿关节炎模型，其中marks和JAK-STAT通路之间的连接是由miRNAs介导的。我们从生物学和病理学的角度全面概述了MARCKS的结构、分子特征和功能，并将讨论这一途径的临床意义。
The myristoylated alanine-rich C-kinase substrate (MARCKS) and the MARCKS-related protein (MARCKSL1) are ubiquitous, highly conserved membrane-associated proteins involved in the structural modulation of the actin cytoskeleton, chemotaxis, motility, cell adhesion, phagocytosis, and exocytosis. MARCKS includes an N-terminal myristoylated domain for membrane binding, a highly conserved MARCKS Homology 2 (MH2) domain, and an effector domain (which is the phosphorylation site). MARCKS can sequester phosphatidylinositol-4, 5-diphosphate (PIP2) at lipid rafts in the plasma membrane of quiescent cells, an action reversed by protein kinase C (PKC), ultimately modulating the immune function. Being expressed mostly in innate immune cells, MARCKS promotes the inflammation-driven migration and adhesion of cells and the secretion of cytokines such as tumor necrosis factor (TNF). From a clinical point of view, MARCKS is overexpressed in patients with schizophrenia and bipolar disorders, while the brain level of MARCKS phosphorylation is associated with Alzheimer’s disease. Furthermore, MARCKS is associated with the development and progression of numerous types of cancers. Data in autoimmune diseases are limited to rheumatoid arthritis models in which a connection between MARCKS and the JAK-STAT pathway is mediated by miRNAs. We provide a comprehensive overview of the structure of MARCKS, its molecular characteristics and functions from a biological and pathogenetic standpoint, and will discuss the clinical implications of this pathway.
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影响因子：
4
作者：
Disatnik, MH;Boutet, SC;Rando, TA
通讯作者：
Rando, TA
影响因子：
--
作者：
Dorris E;O'Neill A;Hanrahan K;Treacy A;Watson RW
通讯作者：
Watson RW
影响因子：
11.4
作者：
BROOKS, SF;HERGET, T;ROZENGURT, E
通讯作者：
ROZENGURT, E
DOI：
10.1016/0165-3806(96)00097-1
发表时间：
1996-10-23
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Blackshear, PJ;Lai, WS;Sulik, KK
通讯作者：
Sulik, KK
影响因子：
4.3
作者：
Chun, Kwang-Rok;Bae, Eun Mi;Lee, Won-Ha
通讯作者：
Lee, Won-Ha