Putting the rap on integrin activation.
Putting the rap on integrin activation.
复制标题
对整合素激活进行批评。
DOI：
10.1016/s0167-5699(00)01783-7
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Y. Shimizu
中科院分区：
文献类型：
--
作者：
Y. Shimizu
如今，很难找到不受 Ras 和 Rho 家族众多 GTP 酶调节的细胞反应。大量膜受体可以激活这些细胞内开关，从而产生多种下游细胞反应，包括肌动蛋白细胞骨架的调节。尽管科学界的焦点一直集中在有限数量的 GTP 酶上，包括 H-ras、Rac、Rho 和 cdc42，但其他 GTP 酶现在也越来越受到重视。其中之一是 Rap1，它是 Ras 样 GTP 酶家族中普遍表达的成员，在血小板、中性粒细胞和大脑中含量特别丰富。尽管 Rap1 已被提议作为 Ras 信号传导的拮抗剂，但最近的研究表明 Rap1 可以独立于或不同于 Ras 启动的信号事件启动信号事件。最近的三篇论文强调了 Rap1 在调节整合素粘附受体功能活性方面的一个潜在功能。在某些方面与 GTP 酶本身类似，整合素可以在不同的功能活性状态之间来回循环。特别是在白细胞和血小板上表达的整合素保持在相对不活跃的状态，直到外部刺激导致整合素介导的粘附迅速增加，而这不需要增加细胞表面的整合素表达。早期研究表明 R-ras 和 H-ras 在整合素激活中具有积极或消极的作用。我们现在可以添加 Rap1 作为另一种能够调节整合素激活的 GTP 酶。 Caron 等人[1]、Katagiri 等人[2]和里德奎斯特等人[3]证明 Rap1 的激活足以增强巨噬细胞、前 B 细胞系、T 细胞和 HL-60 细胞中 β2 整合素介导的粘附。更重要的是，抑制内源性 Rap1 功能可阻断 αMβ2 介导的由佛波醇 12-肉豆蔻酸酯 13-乙酸酯 (PMA)、脂多糖 (LPS)、肿瘤坏死因子 a (TNF-α) 或血小板激活因子 (PAF)[1] 诱导的 C3bi 调理靶标的吞噬作用，通过 T 细胞受体连接激活白细胞功能相关抗原 1 (LFA-1) 整合素[2] 或 CD31 连接 [3]，以及 PMA 诱导的 HL-60 细胞聚集 [2]。
These days, it is hard to find a cellular response that is not regulated by the many GTPases of the Ras and Rho families. A large array of membrane receptors can activate these intracellular switches, resulting in a diverse array of downstream cellular responses, including regulation of the actin cytoskeleton. Although the scientific spotlight has been focused on a limited number of GTPases, including H-ras, Rac, Rho and cdc42, other GTPases are now gaining prominence. One of these is Rap1, a ubiquitously expressed member of the Ras-like family of GTPases that is particularly abundant in platelets, neutrophils and the brain. Although Rap1 has been proposed to function as an antagonist of Ras signaling, recent studies suggest that Rap1 can initiate signaling events independent of, or distinct from, those initiated by Ras. Three recent papers highlight one potential function for Rap1 in regulating the functional activity of integrin adhesion receptors.Similar in some ways to GTPases themselves, integrins can cycle back and forth between different states of functional activity. Integrins expressed on leukocytes and platelets in particular are maintained in a relatively inactive state until an external stimulus results in a rapid increase in integrin-mediated adhesion that does not require increased integrin expression on the cell surface. Earlier studies suggested either positive or negative roles for R-ras and H-ras in integrin activation. We can now add Rap1 as another GTPase capable of regulating integrin activation. Caron et al.[1], Katagiri et al.[2] and Reedquist et al.[3] demonstrated that activation of Rap1 was sufficient to enhance β2 integrin-mediated adhesion in macrophages, a pro-B cell line, T cells and HL-60 cells. More significantly, inhibition of endogenous Rap1 function blocked αMβ2-mediated phagocytosis of C3bi-opsonized targets induced by phorbol 12-myristate 13-acetate (PMA), lipopolysaccharide (LPS), tumor necrosis factor a (TNF-α) or platelet activating factor (PAF)[1], activation of leukocyte function-associated antigen 1 (LFA-1) integrin by T-cell receptor ligation [2] or CD31 ligation [3], and PMA-induced aggregation of HL-60 cells [2].