在细胞生物学研究中使用的化学激活剂和抑制剂的综述。
A comprehensive review of chemical activators and inhibitors used in cell biology research.
细胞生物学研究细胞结构、生理特性及细胞功能。它涉及到对细胞器、细胞与周围环境间相互作用、生命周期、分化及死亡的研究。细胞生物学与遗传学、分子生物学、发育生物学和生物化学等其它生物学领域是密切相关的。
对于细胞生物学领域的研究者而言,为了更加全面地理解细胞的功能、细胞的信号传递以及控制细胞命运、功能及表型的胞内机制,抑制剂与激活剂是至关重要的研究工具。许多抑制剂和激活剂都被广泛用于研究细胞动力学及功能。这里我们对真核细胞中各种细胞生物学研究如细胞内吞、分泌、粘附、细胞骨架动力学、内质网和高尔基体研究中常用的抑制剂和激活剂进行了综述。
细胞骨架为细胞提供了特定的结构与形状。真核细胞主要有三种细胞骨架纤维:1)微丝,2)中间丝和3)微管。
- 微丝(肌动蛋白丝):这是细胞骨架中最细的纤维。它们由肌动蛋白亚基的线性聚合物所组成,通过在纤维一端的伸长并伴随着另一端的收缩来产生力,从而使其间的纤维产生净移动。
- 中间丝:这种纤维的平均大小为直径10纳米并且比肌动蛋白丝更稳定(是紧密结合的),是细胞骨架的异质成分。中间丝负责组织细胞内部的三维结构和细胞器,是核纤层的结构性组成部分。它们也参与一些细胞-细胞间和细胞-基质间的连接过程。
- 微管:它们是直径为23nm的空心圆柱,大多数情况下由13条原纤维组成,而这些原纤维则是alpha微管蛋白和beta微管蛋白的聚合物。它们具有很高的动态活性,通过结合GTP来进行聚合反应并通常由中心体来组织。
抑制剂 | 靶点 | 机制 | 作用特点及效果 | 参考文献、来源及供应商 |
---|---|---|---|---|
细胞松弛素D(C30H37NO6) | 肌动蛋白 | 结合于肌动蛋白核和F-肌动蛋白的生长端,从而抑制聚合反应。诱导肌动蛋白解聚。 | 溶于DMSO和乙醇。抑制收缩。抑制依赖于p-53的细胞通路。引起G1-S转化过程中的细胞周期阻滞。抑制胰岛素刺激的葡萄糖转运。 | [1-3], Sigma-Aldrich, EMD/Millipore, Tocris Bioscience, Enzo Life Science, Invitrogen, Santa Cruz Biotechnology, Cayman Chemical |
Lantraculin A(C22H31NO5S) | 肌动蛋白 | 扰乱微丝介导的过程。与G-肌动蛋白单体形成1:1的复合物(Kd = 200 nM)。 | 溶于DMSO和乙醇。比细胞松弛素的抑制效果强10-100倍。抑制巨噬细胞的吞噬作用。比Lantraculin B的效果更强。 | [1-4], Invitrogen, Tocris Bioscience, Sigma-Aldrich, Cayman Chemical, Santa Cruz Biotechnology, EMD/Millipore |
Lantraculin B(C20H29NO5S) | 肌动蛋白 | 体外反应中抑制肌动蛋白的聚合(Kd = 60 nM)。扰乱微丝的组织和微丝介导的过程。 | 溶于DMSO、甲醇或乙醇。比细胞松弛素的抑制效果强10-100倍。在该复合物持续存在的情况下被血清缓慢失活并导致短暂的诱导变化。 | [5-7], Invitrogen, Sigma-Aldrich, Cayman Chemical, Santa Cruz Biotechnology, EMD/Millipore, Enzo Life Science |
Wiskostatin(C17H18Br2N2O) | 肌动蛋白 | 选择性地抑制N-WASP(Wiskott-Aldrich综合症蛋白(WASp)家族成员)并抑制Arp2/3复合物的活化。该分子阻断肌动蛋白丝的组装。 | 在DMSO中溶解度可达100 mM。同样抑制PIP2诱导的肌动蛋白聚合反应(EC50 ~ 4μM)。抑制依赖于肌动蛋白的细胞功能(迁移、运输、吞噬、内褶)。 | [8-10], Affix Scientific, Enzo Life Science, Sigma-Aldrich, Tocris Bioscience |
Mycalolide B(C52H74N4O17) | 肌动蛋白 | 它选择性地将F-肌动蛋白彻底解聚成G-肌动蛋白。 与肌动蛋白以1:1的摩尔比进行结合(Kd=13-20 nM)。 | 溶于DMSO、甲醇或异丙醇。抑制肌动球蛋白ATP酶。 | [11-13], Santa Cruz Biotechnology, Enzo Life Science |
Nocodazole(C14H11N3O3S) | 微管 | 抑制微管的动态变化并促使微管解聚。与β微管蛋白结合并阻止两个链间二硫键中任意一个的形成。 | 在DMSO的溶解度达10 mg/ml。有丝分裂抑制剂。将细胞周期阻滞在G2/M期。抑制各种癌症相关的激酶,包括ABL、c-KIT、BRAF、MEK1、MEK2和MET。 | [14-17], Sigma-Aldrich, Tocris Bioscience, Cell Signaling Technology, EMD/Millipore |
长春碱(C46H58N4O9 · H2SO4) | 微管 | 解聚微管。与微管蛋白结合并诱导其自缔形成螺旋形聚合体,抑制微管组装。 | 溶于水和甲醇。通过阻断有丝分裂纺锤体的形成将细胞周期阻滞于G2/M期。在一些肿瘤细胞系中诱导凋亡。抑制自噬体的成熟。 | [16, 18, 19], Sigma-Aldrich, Tocris Bioscience, EMD/Millipore, Santa Cruz Biotechnology。 |
秋水仙碱(C22H25NO6) | 微管 | 与微管蛋白结合并阻止其聚合 | 在乙醇中溶解度达50 mg/ml,在水中溶解度可达100 mM,DMSO中溶解度可达100 mM。有丝分裂抑制剂。在一些正常的及癌症细胞系中诱导凋亡 | [20-22], Sigma-Aldrich, Tocris Bioscience, EMD/Millipore |
长春新碱(C46H56N4O10 · H2SO4) | 微管 | 能与微管蛋白结合并抑制微管形成的吲哚生物碱。解聚微管。 | 溶于甲醇和水。延迟细胞周期的进程。在人类淋巴瘤细胞中诱导凋亡。 | [23-25], Sigma-Aldrich, Tocris Bioscience, EMD/Millipore, Santa Cruz Biotechnology。 |
激活剂 | 靶点 | 机制 | 作用特点及效果 | 参考文献、来源及供应商 |
---|---|---|---|---|
Jasplakinolide(C36H45BrN4O6) | 肌动蛋白 | 在体外诱导肌动蛋白聚合及稳定。在体内同样诱导肌动蛋白单体聚合成F-肌动蛋白。 | 在DMSO中溶解度>2 mg/ml。一种具有杀菌、杀虫、抗癌特性的环羧酚酸肽。无荧光且具有细胞透性的F-肌动蛋白。 | [26-29], Sigma-Aldrich, EMD/Millipore, Santa Cruz Biotechnology, Invitrogen, Tocris Bioscience |
紫杉醇(Taxol)(C47H51NO14) | 微管 | 结合于β-微管蛋白的N端,促进微管组装并抑制微管蛋白分解 | 溶于DMSO和甲醇。抗肿瘤和抗白血病试剂。将细胞周期阻止于G2/M期。导致异常的有丝分裂并且有时会引起凋亡。 | [30-32], Sigma-Aldrich, EMD/Millipore, Cell Signaling Technolgy, Cytoskeleton Inc. |
鬼笔环肽(C35H48N8O11S) | 肌动蛋白 | 与聚合的F-肌动蛋白结合并保持其稳定,防止解聚的发生(F-肌动蛋白转变为G-肌动蛋白) | 溶于乙醇和甲醇。从真菌中分离出的有毒双环七肽。干扰富含肌动蛋白的结构行使功能。鬼笔环肽的偶联物被用作确认纤维状肌动蛋白的探针。 | [33-35], Sigma-Aldrich, EMD/Millipore, Tocris Bioscience, Santa Cruz Biotechnology, Enzo Life Science |
内质网(ER)是真核生物中一种会形成互连的膜囊泡网络的细胞器。它参与了细胞物质的合成、修饰和运输。它从细胞膜开始伸展,经过细胞质,一直与核膜相连。取决于细胞类型、细胞功能和细胞需求,内质网具有多种不同的功能。在结构与功能上,它由两种区域组成。
- 粗面内质网:它是一系列扁平状囊泡且胞浆侧由核糖体组成。核糖体是细胞中的蛋白质合成位点。粗面内质网加工膜及分泌蛋白,在某些白细胞中产生抗体,而在胰腺细胞中产生胰岛素。其它功能还包括组装过程中的起始N-糖基化和溶酶体酶的加工。
- 滑面内质网:它是一个光滑的微管网络并且不包含核糖体。它通常与粗面内质网相连,是那些负责将内质网产物运输到不同位点的囊泡的过渡区域。它具有多种功能,包括脂质合成、碳水化合物代谢、钙离子浓度调节、药物解毒和受体附着到细胞膜蛋白。在肌肉中,滑面内质网辅助肌肉细胞的收缩,在脑细胞中则合成雄性和雌性荷尔蒙。
内质网应激:内质网介导的蛋白折叠一旦失衡就会引起内质网应激。内质网的应激信号传导通路或应激响应被称作未折叠蛋白反应(UPR)。最初的UPR只是尝试通过停止蛋白翻译并激活可增加参与蛋白折叠的分子伴侣的信号通路来恢复细胞的正常运作。当UPR的这种初始尝试失败而扰乱还在持续的情况下,UPR就会开始诱导凋亡。
下面提到的抑制剂是用于抑制内质网功能或诱发内质网应激的,而提到的激活剂则用于诱导内质网功能或抵抗内质网应激的:
抑制剂 | 靶点 | 机制 | 作用特点及效果 | 参考文献、来源及供应商 |
---|---|---|---|---|
Eeyarestatin I(C27H25Cl2N7O7) | 内质网相关蛋白降解(ERAD) | 靶向p97相关的去泛素化过程(PAD)并抑制依赖于ataxin-3(atx3)的去泛素化过程。抑制内质网中Sec61介导的蛋白质转运。 | 在DMSO中溶解度达100mM,在乙醇中溶解度达5mM。在淋巴样细胞系、BJAB、HBL-2、JEKO-1、Jurkat、KMS-12、MINO以及慢性淋巴细胞白血病中的原代白血病细胞中诱发细胞毒性。通过促凋亡蛋白NOXA诱导细胞死亡。 | [36-40], Sigma-Aldrich, EMD/Millipore, Tocris Bioscience, Santa Cruz Biotechnology |
DBeQ(C22H20N4) | 内质网相关蛋白降解途径 | 以可逆且ATP竞争性的方式(Ki = 3.2 µM)抑制ATP酶p97活性(对于野生型或C522A p97的IC50 = 1.6 µM) | DMSO中溶解度达100 mM。在RPMI8226、HeLa和HEK29细胞中抑制细胞增殖。抑制caspase 3/7活性及凋亡。 | [41, 42], Sigma-Aldrich, EMD/Millipore, Tocris Bioscience, BioVision Inc. |
Xestospongin C(C28H50N2O2) | 血管舒缓激肽和内质网的钙外流 | 可逆地抑制内质网钙库中的血管舒缓激肽-和氨甲酰胆碱-Ca2+外流。 | 溶于DMSO、乙醇和甲醇。大环双-1-oxaquinolizidine的合成形式。具有膜通透性。可逆地抑制IP3受体。 | [43-45], Sigma-Aldrich, EMD/Millipore, Cayman Chemicals, Tocris Bioscience |
Kifunensine(C8H12N2O6) | 内质网相关蛋白降解(ERAD) | 抑制内质网相关的甘露糖苷酶活性。 | 水(双蒸热水)中溶解度达50 mM。生物碱化合物。选择性抑制负责加工I类糖蛋白的α-甘露糖苷酶。 | [46, 47], Sigma-Aldrich, EMD/Millipore, Cayman Chemicals, Tocris Bioscience, Santa Cruz Biotechnology. |
衣霉素(C39H60N4O16) | 蛋白折叠 | 诱导内质网应激。抑制N-糖基化并阻断N-糖苷蛋白-糖类键的形成。 | 溶于DMF、DMSO和吡啶。衣霉素A、B、C和D的混合物。引起G1期阻滞。抑制N-乙酰葡糖胺磷酸转移酶(GPT)。剂量依赖性地抑制DNA合成。 | [48-50], Sigma-Aldrich, Tocris Bioscience, EMD/Millipore, Santa Cruz Biotechnology。 |
毒胡萝卜素(C34H50O12) | 肌浆网Ca2+ ATP酶(SERCA) | 抑制肌浆网Ca2+-ATP酶。抑制自噬过程并诱发内质网应激。 | 溶于DMSO和乙醇。可渗透细胞。诱导凋亡。被用于诱导哺乳动物细胞自噬。 | [51-53], Sigma-Aldrich, EMD/Millipore, Tocris Bioscience. |
ERO1抑制剂I, Erodoxin(C7H5BrN2O5) | 内质网氧化酶1抑制剂 | 选择性抑制酵母内质网氧化酶1(ERO1)。对小鼠ERO1α(IC50 = 400 µM)抑制较弱 | 溶于DMSO。体外抑制依赖于ERO1的硫氧还蛋白-1(Trx1)氧化活性。与参与蛋白折叠、糖基化和细胞壁合成的基因聚类。 | [54], EMD/Millipore |
兔抗内质网蛋白72(623-638)多克隆抗体 | 识别小鼠大脑、脾脏、睾丸和大鼠脑、肌肉、脾、睾丸组织中~72 kDa的ERp72蛋白。以及人宫颈上皮细胞(HeLa)、人成纤维细胞(A431)、人胸腺细胞(Hs67)和小鼠成纤维细胞(3T3)的细胞裂解物。 | [55-57], EMD/Millipore, US Biological, Novus Biologicals. |
激活剂 | 靶点 | 机制 | 作用特点及效果 | 参考文献、来源及供应商 |
---|---|---|---|---|
5,8,11-二十碳三炔酸(C20H28O2) | 在MDCK细胞中引发Ca2+从内质网中释放。 | 引起Ca2+从内质网、线粒体和其它浓度达30 µM的钙库中释放出来 | 乙醇中溶解度达25mg/ml,DMSO中溶解度达25mg/ml或溶于二甲基甲酰胺。脂肪氧化酶的抑制剂。在较高浓度下抑制环氧合酶。 | [58, 59], Sigma-Aldrich, Cayman Chemicals, Enzo Life Sciences |
Salubrinal(C21H17Cl3N4OS) | 防止内质网应激 | 保护细胞免受内质网应激所诱导的凋亡(EC50 ~ 15 μM)。 | 溶于DMSO。选择性抑制使真核翻译启动因子2亚基α(eIF-2α)去磷酸化的磷酸酶复合体 | [60-62], Tocris Bioscience, Santa Cruz Biotechnology, EMD/Millipore. |
牛磺脱氧胆酸(TUDCA)(C26H44NaNO6S) | 抵抗内质网应激 | 抑制内质网应激。 | 溶于水。被用作去垢剂来使脂质和膜结合蛋白增溶。 | [60-62], Sigma Aldrich, Santa Cruz Biotechnology, EMD/Millipore. |
高尔基体是真核细胞中的一种细胞器,是细胞内膜系统的一部分。高尔基体长约1 µM,并由两部分组成:被称为潴泡的扁平膜囊和膜封闭的小泡。它在各种蛋白分泌前的加工过程中起着重要的作用。
高尔基体的各种功能包括:它从来自粗面内质网、含有蛋白质的囊泡处接收蛋白并进行进一步修饰。细胞合成的各种大分子在分泌前或被送到各自目的地之前,都由它负责修饰、富集、分类及包装。它通过加入糖基和磷酸基团来对蛋白修饰。它在动物细胞胞外基质的蛋白聚糖合成中起着重要作用。植物细胞壁中的多糖合成位点。
抑制剂 | 靶点 | 机制 | 作用特点及效果 | 参考文献、来源及供应商 |
---|---|---|---|---|
1,3-环己烷双甲胺(CBM)(C6H10(CH2NH2)2 ) | 通过高尔基体运输到质膜。 | 在体内和体外都可以抑制外被体蛋白与高尔基体膜结合以及完整细胞的分泌 | 溶于乙醇和乙醚 | [63-65], Sigma-Aldrich, Fisher Scientific |
布雷菲德菌素A(BFA)(C16H24O4) | 膜运输、高尔基体 | <40 ng/ml时在许多哺乳动物细胞系中引起高尔基体解体和内质网肿胀 | 溶于甲醇。可逆地阻断蛋白质从内质网(ER)向高尔基体的转运。高密度脂蛋白-介导的胆固醇外流的抑制剂。介导人肿瘤细胞凋亡。 | [66-68], Sigma-Aldrich.Alomone Labs, Tocris Bioscience, Cell Signaling Technology, EMD/Millipore. |
Golgicide A(C17H14F2N2) | 组装和运输 | 通过结合在Arf1和GBF1 Sec7功能域间形成的界面裂缝中选择性地可逆抑制顺面高尔基体ArfGEF GBF1。Arf属于Ras GTP酶家族并介导囊泡运输。 | 溶于DMSO(>10 mg/ml)。导致高尔基体和反面高尔基网的解体与分散。抑制可溶性的和膜结合的蛋白质分泌。 | [69, 70] Sigma-Aldrich, Tocris Bioscience, Santa Cruz Biotechnology, EMD/Millipore |
1-Deoxymannojirimycin(DMM)(C6H13NO4·HCl) | 糖蛋白加工 | 抑制N-糖基化。抑制甘露糖苷酶I。 | 溶于乙醇和水。用于高尔基体介导的糖蛋白加工过程的研究。 | [71-73], EMD/Millipore, Sigma-Aldrich, Tocris Bioscience, Santa Cruz Biotechnology. |
分泌是指细胞或腺体产生和释放一种有用的物质,包括激素、酶、细胞因子和细胞外基质蛋白。该过程中物质被包装进囊泡然后以胞吐方式从细胞中分泌出来。
- 分泌途径:在真核细胞中,经典的分泌过程是通过内质网、高尔基体和其它细胞内囊泡来实现的,是一个由细胞严格调控的过程。广义上来说,要输送出去的蛋白被核糖体合成后停靠在内质网上进行转运。然后含有正确折叠的蛋白的囊泡进入高尔基体。糖基化修饰后进一步进行翻译后修饰。然后蛋白质进入分泌囊泡,沿着细胞骨架移至细胞边缘。最后一步就是囊泡在一个被称为融合孔的结构处与细胞膜融合并进行胞吐,蛋白就被释放到环境中。
- 非经典的蛋白质分泌途径:有许多蛋白不是通过牵涉到内质网和高尔基体的经典途径来分泌的,相反是利用各种不同的非经典的蛋白质分泌途径来分泌的。这些蛋白包括FGF-1(aFGF)、FGF-2(bFGF)和白细胞介素-1(IL1) [74, 75] 。
非经典的分泌机制大致可分为两种。1) 直接使物质跨过胞质蛋白的质膜进行转运,例如FGF2的分泌。2) 胞内转运中间物,例如酰基辅酶A结合蛋白的分泌 [76] 。
抑制剂 | 靶点 | 机制 | 作用特点及效果 | 参考文献、来源及供应商 |
---|---|---|---|---|
CP-10447(C16H13BrN2O) | 载脂蛋白B(apoB)分泌 | 抑制微粒体甘油三酯转移蛋白(MTP, MTTP)并刺激apoB的早期内质网降解 | 溶于DMSO(≥10 mg/ml)。抑制甘油三酯分泌而不影响其合成。人体肝脏微粒体甘油三酯转运活性的有效抑制剂。 | [77-79], Sigma-Aldrich, Pfizer |
Exo 1(C15H12NFO3) | 胞吐 | 在哺乳动物细胞中通过诱导高尔基体膜解体和成管以及重新运输回内质网来可逆地抑制从内质网到高尔基体间的囊泡运输。 | 溶于DMSO、DMF、甲醇或乙醇。它的影响仅限于高尔基体,不能影响其它的内吞细胞器。活化高尔基ARF 1(ADP核糖基化因子)GTP酶。 | [80], Sigma-Aldrich, EMD Millipore |
Exo 2(C18H18N4O2S) | 胞吐 | 类似于BFA但是选择性更强。可能的靶点包括TGN(反面高尔基网)、高尔基体和一部分早期内涵体 | 溶于DMSO(>20 mg/ml)。抑制志贺毒素运送到内质网。作为胞内运输的一种化学探针。 | [81-83], Sigma-Aldrich, Santa Cruz Biotechnology |
生长激素抑制素(C76H104N18O19S2) | 生长激素、胰岛素和胰高血糖素 | 抑制生长激素、胰岛素和胰高血糖素的内源性肽 | 溶于5%乙酸,水中溶解度为0.30 mg/ml。它是一个环状十四肽。同样抑制电压门控Ca2+通道。 | [84-86], Tocris Bioscience, Sigma-Aldrich, EMD/Millipore |
奥曲肽(C49H66N10O10S2) | 胃肠胰肽激素和生长激素 | 它是一个合成的较长作用八肽,是生长激素抑制素的类似物。 | 溶于水 | [87, 88], Sigma-Aldrich, Bachem, Tocris Bioscience |
SXN101742,一种定向分泌抑制剂(TSI) | 生长激素 | 它靶向于GHRH(生长激素释放激素)受体并使参与GH(生长激素)胞吐过程的SNARE蛋白耗尽。 | TSI是来自于肉毒毒素(BoNTs)的重组蛋白。 | [89, 90], Syntaxin Ltd. |
抗FGF1抗体 | 酸性成纤维细胞生长因子(aFGF) | 酸性成纤维细胞生长因子抗体/Beta血管内皮细胞生长因子抗体。产自于兔子或小鼠。与人反应。其应用包括WB、ELISA、IHC-P及中和。用于各种应用的方法及浓度请参考生产商的操作流程 | [91-94], Sigma-aldrich, Abcam, Origene, Thermo Scientific. |
激活剂 | 靶点 | 机制 | 作用特点及效果 | 参考文献、来源及供应商 |
---|---|---|---|---|
α-蛛毒素 | 诱导胞吐 | 与蛛毒素受体结合。利用Ca2+依赖性和非依赖性的作用机制。 | 溶于50%甘油。引起神经递质的释放。导致Ca2+非依赖性的胰岛素胞吐。刺激皮质星形胶质细胞培养物中Ca2+非依赖性的GABA和谷氨酸释放。 | [95-97], Alomone Labs, EMD/Millipore, Enzo Life Sciences |
那格列奈(C19H27NO3) | 胰岛素 | 通过增加胞浆中Ca2+浓度来引起胰腺β-细胞中的胰岛素分泌。 | 溶于DMSO(>5 mg/ml)。它是Kir6.2/SUR1通道的抑制剂。刺激ATP敏感性钾通道依赖性和非依赖性胰岛素分泌。降血糖药。 | [98-101], Sigma-Aldrich, Tocris Bioscience, TCI America |
血管紧张素II(C50H71N13O12) | 醛固酮 | 导致肾上腺中的醛固酮释放 | 溶于水或5%乙酸。刺激血管生成并增加微血管密度。有很强的血管收缩效果。在血管平滑肌细胞中活化p60c-src和ERK1/2、JNK及p38丝裂原活化蛋白激酶。 | [102-104], Sigma-Aldrich, Calbiochem/ EMD/Millipore. |
甲苯磺丁脲(磺脲类)(C12H18N2O3S) | 胰岛素 | 通过直接作用于胰腺β细胞中的ATP敏感性钾通道引起胰岛素释放 | 溶于DMSO或100%乙醇。被CYP2C9(甲苯磺丁脲羟化酶)所代谢 | [105-108], Santa Cruz Biotechnology, Sigma-Aldrich, Abcam. |
瑞格列奈(C27H36N2O4) | 胰岛素 | 关闭胰腺β细胞质膜上的ATP敏感性钾(KATP)通道 | 在DMSO中溶解度达100 mM,在乙醇中溶解度达100 mM。体内具有降血糖效果。 | [109-112], Sigma-Aldrich, Tocris Bioscience |
油酸钠(CH3(CH2)7CH=CH(CH2)7COONa) | 载脂蛋白B100(Apo-B) | 增加肝脏中的载脂蛋白B100分泌 | 溶于水(100 mg/ml)、甲醇(50 mg/ml)和乙醇。激活肝细胞中的蛋白激酶C(PKC)。在较高生理剂量下抑制载脂蛋白B100分泌。 | [113, 114], Santa Cruz Biotechnology, Sigma-Aldrich, TCI America |
分泌素(C130H220N44O40) | 胰液 | 刺激富含碳酸盐的胰液分泌 | 溶于5%的乙酸或水。它是一种强碱性胃肠肽类激素。放松平滑肌。引起胰管线中剂量依赖性的cAMP积累。 | [115-117], Sigma-Aldrich, EMD/Millipore |
细胞通过内陷产生的囊泡从膜上脱落来吸收大分子和溶质的过程被称为“内吞”。内吞可大致分为两类:1)吞噬和2)胞饮。吞噬是特定细胞摄取大颗粒。胞饮是所有细胞中都发生的摄入液体和溶质过程。当泛指细胞内化时,“吞噬”和“胞饮”多数被用作同义词。主要有三种内吞途径:1)网格蛋白介导的内吞作用,2)胞膜窖介导的内吞作用和3)巨胞饮。在这三种内吞途径中,内化步骤始于质膜内陷并将该膜转变为称作内涵体的封闭囊泡。每个途径都有控制内化的一套分子。
抑制剂 | 靶点 | 机制 | 作用特点及效果 | 参考文献、来源及供应商 |
---|---|---|---|---|
氯丙嗪(C17H19ClN2S · HCl) | 网格蛋白介导的内吞作用 | 引起网格蛋白网络在内涵体膜上的组装并阻止细胞表面上的被膜小窝组装。 | 溶于水和甲醇。抑制钙调蛋白依赖性的环核苷酸磷酸二酯酶和一氧化氮合成酶激活。对白血病细胞具有细胞毒性和抗增殖活性。 | [118, 119], Santa Cruz Biotechnology, Sigma-Aldrich, EMD/Millipore |
金雀异黄素(C15H10O5) | 胞膜窖介导的内吞作用 | 可逆性抑制酪氨酸激酶 | 溶于DMSO。可渗透细胞。抑制表皮生长因子受体激酶。抗血管生成剂。抑制肿瘤细胞增殖。抑制肿瘤细胞分化。体外抑制拓扑异构酶II活性。 | [119-122], Sigma-Aldrich, EMD/Millipore |
β-环糊精(C42H70O35) | 胞膜窖介导的内吞作用 | 清除胆固醇 | 水中溶解度达50 mg/ml。由相同的环状α1,4-糖苷键连接的D-葡萄吡喃糖单元形成的七元环。形成包合物。常用的络合剂。 | [123, 124], Sigma-Aldrich, Fisher Scientific, EMD/Millipore |
盐酸阿米洛利(C6H8ClN7O.HCl.H2O) | 巨胞饮 | 抑制Na+/H+交换。降低膜下pH值。阻止Rac1和Cdc42的信号传导。 | S水中溶解度达50 mg/ml。T-型钙通道阻滞剂。抑制尿激酶纤溶酶原激活物(uPA)。抑制血管生成。 | [125-127], Sigma-Aldrich, Tocris Bioscience, EMD4Bioscience, Alomone Labs |
Dynasore(C18H14N2O4) | 网格蛋白介导的内吞作用中的动力蛋白 | 抑制动力蛋白1和2的GTP酶活性(IC50 ~15 µM)。 | 溶于DMSO和乙醇。同样抑制Drp1(线粒体)。会引起纤维化并在胸膜间皮细胞中诱导PAI-1。抑制BSC1细胞的细胞铺展和迁移。 | [128-130], Sigma-Aldrich, Tocris Bioscience, Santa Cruz Biotechnology, EMD4Bioscience, Abcam |
非律平(C35H58O11) | 胞膜窖介导的内吞作用 | 与膜上的胆固醇结合并形成超微机构聚集与复合。 | 非律平由4个异构的多烯大环内酯组成。非律平III是主要成分。抗生素和抗真菌。抑制朊蛋白(PrP)的内吞。 | [123, 131-133], Cayman Chemical, Sigma-Aldrich, Santa Cruz Biotechnology. |
制霉菌素(C47H75NO17) | 胞膜窖介导的内吞作用 | 胆固醇隔离。 | 溶于DMSO、DMF、乙醇和甲醇。抗微生物(酵母、支原体)。增加Na+ - K+泵活性。 | [134-136], Sigma-Aldrich, EMD4Bioscience, Invitrogen |
莫能菌素(C36H61O11。 Na) | 内涵体成熟 | 阻止内涵体酸化 | 溶于氯仿、乙醇和甲醇。聚醚类抗生素。Na+离子载体。阻断糖蛋白分泌。阻断神经酰胺在高尔基体中的运输 | [137-140], Sigma-Aldrich, EMD/Millipore, Enzo Life Sciences |
磷酸氯喹(C18H26ClN3·2H3PO4) | 内涵体成熟 | 它是一种可以装入内涵体和溶酶体这样的酸性囊泡的弱碱,从而抑制内涵体酸化和溶酶体酶活性。 | 水中溶解度达100 mM。内涵体Toll样受体抑制剂(拮抗剂)。在许多癌症细胞系中抑制细胞生长并诱导细胞死亡。 | [128, 139, 141], Sigma-Aldrich, Tocris Bioscience, Imgenex |
渥曼青霉素(C23H24O8) | 巨胞饮 | 抑制磷脂酰肌醇-3激酶(PI3激酶)(IC50 = 5nM) | 溶于DMSO。具有细胞通透性。在很高浓度时抑制肌球蛋白轻链激酶和PI4激酶活性。抑制polo样激酶1(PLK1)(IC50 = 5.8 nM)。 | [142-145], Cell Signaling Technology, Sigma-Aldrich, Tocris Bioscience, EMD/Millipore |
激活剂 | 靶点 | 机制 | 作用特点及效果 | 参考文献、来源及供应商 |
---|---|---|---|---|
佛波醇-12-十四酸酯-13-乙酸酯(PMA)(C36H56O8)(佛波酯) | 巨胞饮 | 在体内和体外都激活蛋白激酶C。诱导膜转运和酶激活。 | DMSO中可溶解至100 mM,在乙醇中可溶解至10 mM。具有感光性。强力的肿瘤诱发物 | [146-148], Sigma-Aldrich, Enzo Life Sciences, Tocris Bioscience, Abcam |
12-O-十四烷酰佛波醋酸酯-13(TPA)(C36H56O8)(佛波酯) | 内吞作用 | 结合并激活蛋白激酶C | 溶于DMSO和乙醇。具有感光性。强力的肿瘤诱发物。人单核U937细胞中诱导凋亡。 | [149-152], Sigma-Aldrich, Cell signaling technology |
核运输主要是通过核孔复合物(NPC)进行的。离子和小分子是通过被动扩散穿越NPC来进行转运的。较大核蛋白质、RNA及核糖核蛋白的输入由核定位信号(NLS)介导停靠于核孔。另一方面,核输出是由核输出信号(NES)介导的。
核输入途径大致由四步组成:1)在输入物、输入蛋白α和输入蛋白β间形成三聚复合物,2)将复合物停靠于NPC(核孔复合物),3)通过中央通道进行转位,4)复合物解离并将输入物释放到核质中。
抑制剂 | 靶点 | 机制 | 作用特点及效果 | 参考文献、来源及供应商 |
---|---|---|---|---|
麦胚凝集素(WGA) | 核输入 | 通过直接与核孔相互作用来抑制核蛋白运输。 | 细胞生物学中广泛使用的一种外源凝集素。对N-乙酰-β-D-葡糖胺基和N-乙酰-β-D-葡糖胺寡聚物有亲和性。用于细胞粘附研究。也用于影响淋巴细胞活化及研究基于糖类的治疗方法。 | [153-155], Sigma-Aldrich, Polysciences Inc., Invitrogen |
来普霉素A(C32H46O6) | 核输出 | 直接与CRM1(输出蛋白-1)这一主要的核输出蛋白结合。 | 溶于甲醇和乙醇。来普霉素A和B的性质是很相似的。具有细胞通透性,抗真菌及抗生素。可以诱导野生型ERK5在核内积聚。 | [156, 157], Sigma-Aldrich, Santa Cruz Biotechnology, EMD/Millipore |
来普霉素B(C33H48O6) | 核输出 | 抑制核运输受体Crm1,该蛋白用于识别底物蛋白中被称为核输出序列(NES)的短肽 | 溶于乙醇。抗真菌、抗生素。抗肿瘤细胞毒素。比来普霉素A效力强两倍。受来普霉素B影响的含NES的蛋白包括HIV-1 REV、肌动蛋白、c-Abl、细胞周期蛋白B1、MDM2/p53、MPF、PKA和MEK。 | [158-160], LC labs, Sigma-Aldrich, Cell signaling technology, EMD/Millipore |
Ratjadone A(C28H40O5) | 核输出 | 通过与CRM1共价结合来抑制含有LR-NES(富含亮氨酸的核输出信号)的蛋白 | 溶于含水缓冲液和甲醇。可通透细胞的聚酮。抗生素。与来普霉素B一样有效。抑制扩增。导致肿瘤细胞在G1期发生细胞周期阻滞。 | [161-163], Sigma-Aldrich, EMD/Millipore, Cell signaling technology, Santa Cruz Biotech. |
依维菌素(C48H74O14(22,23-dihydroavermectin B1a)+ C47H72O14 (22,23dihydroavermectin B1b) | 核输入 | 最近被发现对于输入蛋白α/β介导的核输入具有广谱作用 | 抗病毒。对于研究蛋白质核输入十分有用。调节谷氨酸-GABA活化的氯通道。 | [164-166], MP Biomedicals, Sigma-Aldrich, Fisher Scientific |
一般为了诱导核输入会将设计成NLS的肽段结合在输入底物上。另一方面,针对诸如输入蛋白和运蛋白等可以识别NLS的核运输受体而设计的细胞通透性肽被用于抑制核运输 [167] 。
在特定胞内Ca2+浓度下,磷脂酶C(PLC)、蛋白激酶C(PKC)、Rho GTP酶、Rho激酶(RhoA的下游效应蛋白)、肌球蛋白轻链激酶(MLCK)和肌球蛋白轻链磷酸酶(MLCPh)都会参与细胞收缩过程。
MLCK和MLCPh的作用:细胞收缩主要由肌动蛋白和肌球蛋白介导。肌球蛋白轻链的磷酸化会诱发肌动蛋白和肌球蛋白分子之间的相互作用。肌球蛋白轻链的磷酸化是由肌球蛋白轻链激酶(MLCK)活化与肌球蛋白轻链磷酸酶(MLCPh)之间的平衡所决定的。
Rho GTP酶和Rho激酶的作用:细胞通过粘附位点与微环境间的相互作用会活化Rho GTP酶。活化的Rho GTP酶会与丝氨酸/苏氨酸激酶、Rho激酶、ROK及相关的p160ROCK等激酶结合并提高它们的活性。活化的Rho-激酶会抑制肌球蛋白磷酸酶的活性,从而促使肌球蛋白轻链(MLC)磷酸化。
PLC、 Ca2+和PKC的作用 [168] :收缩过程始于磷脂酶C(PLC)活化,从而产生两种第二信使,甘油二酯(DG)和肌醇1,4,5-三磷酸(IP3)。IP3会导致Ca2+从肌质网中释放出来。Ca2+会以两种方式来诱导收缩:1)Ca2+与DG一起激活蛋白激酶C。PKC则通过使L型Ca2+通道和其它调控横桥周期的蛋白发生磷酸化来进一步促进收缩,2)Ca2+与钙调蛋白结合并活化肌球蛋白轻链激酶(MLCK)。
现在用于研究细胞收缩途径的各种抑制剂和激活剂包括:
抑制剂 | 靶点 | 机制 | 作用特点及效果 | 参考文献、来源及供应商 |
---|---|---|---|---|
星孢菌素(C28H26N4O3) | 肌球蛋白轻链激酶(MLCK)、蛋白激酶C(PKC) | 抑制肌球蛋白轻链激酶(IC50 = 1.3 nM)、蛋白激酶C(IC50 = 700 pM) | 溶于DMSO和甲醇。也抑制蛋白激酶A(IC50 = 7 nM)和蛋白激酶G(IC50 = 8.5 nM)。将正常细胞的细胞周期阻滞于G1期检查点。 | [169-171], Cell signaling Technology Inc., Sigma-Aldrich, EMD/Millipore, Tocris Bioscience, Enzo Life Sciences |
Y-27632(C14H21N3O · 2HCl) | ROCK | Rho关联蛋白激酶的可逆选择性抑制剂(p160ROCK的Ki = 140 nM)。同样抑制ROCK-II。这种抑制对于ATP是竞争性的。 | 在水中可溶达14 mg/ml。抑制激动剂诱导的肌球蛋白磷酸化和平滑肌收缩的Ca2+致敏。同样抑制蛋白激酶C相关激酶(IC50 = 600 nM)。已经被发现会阻止凋亡并增加解离的人胚胎干细胞的存活率及克隆效率而不影响其多能性 | [172-175], Sigma-Aldrich, EMD/Millipore, Tocris Bioscience, Stemgent. |
H-1152(C16H21N3O2S.2HCl) | ROCK | 选择性的ATP竞争性rho激酶(ROCK)抑制剂 | 在水中溶达100 mM,在DMSO中溶达50 mM in DMSO。比Y-27632的效力及选择性更强。对于其它丝氨酸/苏氨酸激酶的亲和性较弱(PKA的Ki=630nM,PKC的为9.27m而MLCK的为10.1mM)。 | [176-179], Tocris Bioscience, Enzo Life Sciences, Sigma-Aldrich, Santa Cruz Biotechnology, |
ML-9(C15H17N2O2SCl · HCl) | 肌球蛋白轻链激酶(MLCK)、蛋白激酶C(PKC) | 肌球蛋白轻链激酶(MLCK)(Ki = 4 μM)和PKC(Ki = 54 μM)的选择性抑制剂 | 在DMSO中溶达25 mM。抑制PKA(Ki = 32 μM)。 浓度为10-100 µM时抑制血管平滑肌张力并降低胞内Ca2+浓度。 | [180-182], Tocris Bioscience, Cayman Chemical, Sigma-Aldrich, EMD/Millipore |
ML-7(C15H17IN2O2S · HCl) | 肌球蛋白轻链激酶(MLCK) | 肌球蛋白轻链激酶的ATP竞争性选择抑制剂(Ki = 300 nM) | 溶于DMSO或50%乙醇。在较高浓度时抑制蛋白激酶A(Ki = 21 µM)和蛋白激酶C(Ki = 42 µM)。ML-9的衍生物。与ML-9相比是更加强劲的抑制剂。 | [180, 183, 184], Sigma-Aldrich, Tocris Bioscience, Santa Cruz Biotechnology, EMD/Millipore |
K-252a(C27H21N3O5) | MLCK、PKC | 抑制PKC(IC50 = 32.9 nM)和MLCK(Ki = 20 nM)。作为ATP竞争性抑制剂同样抑制PKA、PKG、CaMK、磷酸化酶激酶、MAP激酶和受体酪氨酸激酶的trk家族。 | 溶于DMF或DMSO。星孢菌素类似物。阻止下游效应蛋白(MAPK、Akt)的自磷酸化与活化。通过抑制Cdc2和Cdc25来引起凋亡和细胞周期阻滞。 | [185-188], LC Laboratories, Tocris Bioscience, EMD/Millipore/Millipore, Invitrogen, Sigma-Aldrich |
三氟拉嗪 | 钙调蛋白 | 钙调蛋白拮抗剂。抑制Ca2+/钙调蛋白依赖性的磷酸二酯酶。 | 吩噻嗪类抗精神病D2多巴胺受体拮抗剂,抑制门控阳离子通道(IC50 = 13 µM)并抑制肝鸟氨酸脱羧酶活性。 | [189] Sigma-Aldrich, EMD/Millipore |
W-7(C16H21ClN2O2S · HCl) | 钙调蛋白 | 抑制Ca2+/钙调蛋白活化的磷酸二酯酶(IC50 = 28 µM)和肌球蛋白轻链激酶(IC50 = 51 µM)。 | 抑制仓鼠卵巢K1细胞增殖 | [190-192], Sigma-Aldrich, EMD/Millipore, Santa Cruz Biotechnology |
激活剂 | 靶点 | 机制 | 作用特点及效果 | 参考文献、来源及供应商 |
---|---|---|---|---|
内皮素I(C109H159N25O32S5) | MLC磷酸化 | 有效的血管收缩剂。 内皮素I通过激活Rho激酶途径以及之后的MLC磷酸化来调节收缩 | 在1%乙酸和水中溶解度 >1mg/ml。诱导缺氧诱导因子1α及VEGF的产生。在表达ETA受体的成纤维细胞中激活PLC。 | [193-196], Sigma-Aldrich, EMD/Millipore, Fisher |
Calpeptin(C20H30N2O4) | Rho GTP酶 | 激活RhoA、B和C。RhoA的激活可能是由于抑制了肌球蛋白轻链磷酸化。 | 溶于DMSO和DMF。它是钙蛋白酶这种Ca2+依赖性的蛋白酶的抑制剂,组织蛋白酶L的有效抑制剂并且优先抑制膜相关酪氨酸磷酸酶活性。 | [197, 198], Cytoskeleton Inc., Santa Cruz Biotechnology, Tocris Bioscience, EMD/Millipore |
佛波醇 12-十四酸酯-13-乙酸酯(PMA)(C36H56O8) | 蛋白激酶C | 与PKC可逆结合 | 光敏的。溶于DMSO和乙醇。甚至在nM浓度时就能在体外和体内激活PKC。它也是强力的肿瘤诱发物。 | [199-201], Sigma-Aldrich, EMD/Millipore |
密执毒素(C38H38O10) | 蛋白激酶C | 在nM浓度时活化蛋白激酶。 | 在乙醇中100%可容。肿瘤诱发物。诱导白细胞介素1α,与植物血凝素一起诱导干扰素。 | [202, 203], Sigma-Aldrich, Santa Cruz Biotechnology |
BAY K 8644(C16H15F3N2O4) | Ca2+通道 | L型Ca2+通道激活剂(EC50 = 17.3 nM) | 溶于甲醇(63 mg/ml)、乙醇(63 mg/ml)和DMSO(20 mg/ml)。抑制自噬。促进β-细胞增殖与再生。 | [204-206] Tocris Bioscience, Sigma-Aldrich, Santa Cruz Biotechnology, EMD/Millipore |
12,13-二丁酸佛波醇(PDBu)(C28H40O8) | 蛋白激酶C | 活化蛋白激酶C | 光敏的。溶于水、DMSO、丙酮、乙醇。由于相对不疏水,比PMA更容易从组织培养中的细胞内清洗出来。引起Na+,K+-ATP酶的磷酸化。也会促使生成一氧化氮。 | [177, 207, 208], Sigma-Aldrich, EMD/Millipore |
细胞粘附:细胞利用细胞粘附分子与胞外基质、其它细胞或细胞培养物的表面发生相互作用并发生粘附。细胞粘附分子(CAM)包括选择素、整合素和钙粘素。每种粘附分子识别不同的分子且功能各异。
细胞-细胞间相互作用:细胞-细胞间粘附主要由钙粘素调节。
细胞-微环境间的相互作用:细胞与ECM(胞外基质)间的粘附主要由整合素调节。
粘着连接见于多种细胞类型,在上皮细胞中十分常见。细胞连接的胞质侧与肌动蛋白细胞骨架相连。此处钙粘素受体通过它们的嗜同种受体反应跨过相邻的质膜。
桥粒是专门用于细胞与细胞间粘附的,常见于源自外胚层的细胞系。它们帮助细胞抵抗机械应力。在上皮、肌肉组织中结合细胞时以及维持皮肤和心脏等器官的完整性中都需要它们 [209, 210] 。半桥粒形式类似桥粒。与将两个细胞结合在一起的桥粒不同的是,半桥粒将细胞与胞外基质相连。
整合素:它们是一个异二聚体的跨膜糖蛋白家族。它们由120-170 kDa的大“α”亚基与90-100 kDa的小“β”亚基组成。由9种β亚基和24种α亚基可以组成各种整合素 [211-214] 。
选择素:它们是结合糖部分的单链跨膜糖蛋白。有3种选择素,即L-、E-和P-选择素。 [215-218] 。
钙粘素:它们是一类依赖钙离子行使功能的1型跨膜蛋白。它们是细胞粘附分子(CAM)的一个超家族并可以分成几个亚类,包括E-、N-和P-钙粘素 [219-222] 。免疫球蛋白超家族(IgSF CAMs):Ig超家族成员包括NCAM(神经细胞粘附分子)、ICAM-1(细胞间黏附分子)、VCAM-1(血管细胞粘附分子)和PECAM-1(血小板内皮细胞粘附分子)。
抑制剂 | 靶点 | 机制 | 作用特点及效果 | 参考文献、来源及供应商 |
---|---|---|---|---|
蛇毒锯鳞蝰素(α1型)(C217H341N71O74S9) | 细胞粘附ECM | 整合素β1和β3 | 水中溶达1 mg/ml。去整合素家族成员。扰乱破骨细胞粘附到骨骼。抑制黑色素瘤细胞及成纤维细胞与纤维粘连蛋白的粘附。抑制血小板聚集。 | [223-226], Sigma Aldrich, Tocris Bioscience |
聚(甲基丙烯酸羟乙酯)(C6H10O3)n | 细胞与组织培养处理过的表面间的粘附。 | 抑制培养容器中细胞粘附到生长表面 | 溶于乙醇。水溶胀性的多聚物。 | [227, 228], Sigma Aldrich, Santa Cruz Biotechnology, Polysciences Inc. |
CyloRGDfV(C26H38N8O7)或RGDS肽 | 细胞与RGD结合 | 它是一种含RGD序列的肽拮抗剂。针对α(V)β(3)整合素。 | 被用于抑制细胞与玻连蛋白和纤维连接蛋白等RGD蛋白结合。 | [229-231], Sigma-Aldrich, Anaspec, GenScript, Tocris Bioscience |
KF 38789(C19H21NO5S) | P-选择素介导的细胞粘附 | 特异性抑制P-选择素介导的细胞粘附(IC50 = 1.97 μM)。 | DMSO中溶达100 mM。 | [232-234], Tocris Bioscience, R&D systems, Santa Cruz Biotechnology |
A 205804(C15H12N2OS2) | 细胞-细胞间粘附(E-selectin、ICAM-1) | 特异性抑制E-选择素和ICAM-1表达。 | DMSO中可溶解至100 mM,在乙醇中可溶解至10 mM。 | [235-237], Tocris Bioscience, R&D systems, Santa Cruz Biotechnology |
A 286982(C24H27N3O4S) | 细胞-细胞间粘附(LFA-1 - ICAM-1) | 抑制LFA-1/ICAM-1相互作用。 | DMSO中溶达100 mM,乙醇中溶达50 mM | [238, 239], Tocris Bioscience, R&D systems, Santa Cruz Biotechnology |
FAK抑制剂14(1,2,4,5-苯四胺四盐酸)(C6H10N4.4HCl) | 细胞粘附(局部粘着斑激酶) | 特异性地抑制局部粘着斑激酶(FAK)。体外抑制细胞粘附。 | 溶于水和DMSO。 | [240], Tocris Bioscience, Sigma Aldrich, Selleck Chemicals, R&D systems, Santa Cruz Biotechnology |
PF 573228(C22H20F3N5O3S) | 细胞粘附(局部粘着斑激酶) | 特异性地抑制局部粘着斑激酶(FAK)(IC50 = 4 nM)。 | 溶于DMSO。阻断血清和纤维连接蛋白介导的定向迁移。非受体酪氨酸激酶抑制剂。 | [241, 242] Tocris Bioscience, Sigma Aldrich, Santa Cruz Biotechnology |
Obtustatin(C184H284N52O57S8) | 细胞粘附(α1β1抑制剂) | 41个氨基酸的去整合素肽,极强的整合素α1β1抑制剂 | 水中溶达2 mg/ml。体内抑制血管生成。不含有经典的RGD序列。 | [243-245], Smartox biotechnology, Tocris Bioscience, R&D systems |
Lebestatin | 整合素介导的细胞粘附 | 去整合素家族成员。 | [243, 246] | |
依替巴肽(C35H49N11O9S2) | 糖蛋白IIa/IIIb | 血小板受体整合素糖蛋白IIb/IIIa | 溶于水。抑制血小板聚集。 | [247], Fisher Scientific, Tocris Bioscience, R&D systems |
激活剂 | 靶点 | 机制 | 作用特点及效果 | 参考文献、来源及供应商 |
---|---|---|---|---|
肽F9(C110H175N31O27S2) | 细胞粘附 | 与肝素结合。 | 溶于水。它是来自于层粘连蛋白B1链上的肝素结合域。 | [248, 249], Tocris Bioscience, R&D systems |
RGD肽 | 细胞粘连 | 与整合素结合 | 用于引导整合素介导的细胞在生物材料、多聚物和纳米颗粒上的粘附。 | [250-252], Santa Cruz Biotechnology, Anaspec, Sigma-Aldrich, Enzo life sciences |
来邦网系统性地调查文献中的抗体和其他试剂,仪器的应用。 至2015年10月17日,2555文章已被查阅, (总共10598篇; 文章的其他部分只查阅抗体的应用)。表15列出这2555的文章引用的活化剂和抑制剂和他们的主要供应商。
化学名 | 总文献数 | 供应商 | 供应商文献数 | 文献|
---|---|---|---|---|
细胞骨架 | ||||
细胞松弛素B | 5 | |||
Sigma | 5 | [253-257] | ||
细胞松弛素D | 5 | |||
Sigma | 4 | [258-261] | ||
Tocris | 1 | [262] | ||
Latrunculin A | 4 | |||
Life Tech/Molecular Probes | 1 | [263] | ||
EMD/Millipore | 1 | [264] | ||
Cayman chemical | 1 | [260] | ||
Sigma | 1 | [265] | ||
Latrunculin B | 4 | |||
BioMol/Enzo | 2 | [262, 266] | ||
EMD/Millipore | 2 | [267, 268] | ||
Nocodazole | 12 | |||
Sigma | 8 | [269-276] | ||
EMD/Millipore | 2 | [261, 277] | ||
Invitrogen | 1 | [278] | ||
Applied Precision | 1 | [279] | ||
紫杉醇(Paclitaxel) | 5 | |||
Sigma | 3 | [280-282] | ||
Calbiochem | 3 | [283] | ||
Cytoskeleton | 3 | [284] | ||
鬼笔环肽(Phalloidin) | 44 | |||
Life Tech | 36 | [258, 278, 285-316] | ||
Sigma | 8 | [317-324] | ||
内质网(Endoplasmic Reticulum) | ||||
Xestospongin C | 1 | |||
EMD/Millipore | 1 | [325] | ||
Kifunensine | 1 | |||
Toronto Research Chemicals | 1 | [326] | ||
衣霉素(Tunicamycin) | 8 | |||
Sigma | 4 | [327-330] | ||
EMD/Millipore | 4 | [262, 331-333] | ||
毒胡萝卜素(Thapsigargin) | 11 | |||
Sigma | 9 | [332-340] | ||
EMD/Millipore | 2 | [262, 331] | ||
高尔基体(Golgi) | ||||
布雷菲德菌素A(Brefeldin A) | 19 | |||
Sigma | 15 | [264, 329, 341-354] | ||
BD Biosciences | 3 | [355-357] | ||
Life Technologies | 1 | [358] | ||
内吞(Endocytosis) | ||||
β-Cyclodextrin | 6 | |||
Sigma | 6 | [259, 304, 359-362] | ||
Filipin | 3 | |||
Sigma | 3 | [363-365] | ||
制霉菌素(Nystatin) | 2 | |||
Sigma | 2 | [366, 367] | ||
莫能菌素(Monensin) | 3 | |||
Sigma | 1 | [368] | ||
BD Biosciences | 1 | [369] | ||
eBioscience | 1 | [370] | ||
磷酸氯喹(Chloroquin) | 5 | |||
Sigma | 5 | [328, 371-374] | ||
渥曼青霉素(Wortmannin) | 9 | |||
EMD/Millipore | 5 | [331, 339, 375-377] | ||
Sigma | 2 | [378, 379] | ||
Enzo | 1 | [380] | ||
Cell Signaling Technologies | 1 | [381] | ||
佛波酯(Phorbol ester ; PMA/TPA) | 37 | |||
Sigma | 28 | [253, 292, 335, 346, 350-352, 356, 369, 382-400] | ||
EMD/Millipore | 6 | [344, 401-405] | ||
Enzo | 1 | [339] | ||
AppliChem | 1 | [406] | ||
Cell Signaling Technology | 1 | [407] | ||
细胞收缩 (Cell Contraction) | ||||
星孢菌素(staurosporine) | 5 | |||
Sigma | 5 | [366, 408-411] |
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