Involvement of microtubules in the control of adhesion-dependent signal transduction
Involvement of microtubules in the control of adhesion-dependent signal transduction
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DOI：
10.1016/s0960-9822(02)70714-8
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发表时间：
1996-10-01
期刊：
影响因子：
9.2
通讯作者：
Geiger, B
中科院分区：
文献类型：
--
作者：
Bershadsky, A;Chausovsky, A;Geiger, B
背景：细胞与细胞外基质（ECM）的黏附产生跨膜信号，这些信号影响细胞的增殖、分化和存活。这些信号由整合素与ECM之间的相互作用触发，涉及特定蛋白质的酪氨酸磷酸化，包括黏着斑激酶（FAK）和桩蛋白，以及黏着斑和肌动蛋白束的组装。在贴附于基质且血清饥饿的瑞士3T3细胞中，黏着斑和肌动蛋白束系统发育不良，FAK和桩蛋白的酪氨酸磷酸化水平较低。许多生长因子能迅速刺激这些蛋白质的酪氨酸磷酸化以及黏着斑和肌动蛋白束的组装。生长因子和与ECM的黏附对于细胞随后进入细胞周期的S期都是必需的。
结果：在血清饥饿的瑞士3T3细胞中，诺考达唑或长春碱破坏微管，在不添加外部生长因子的情况下，诱导黏着斑和微丝束的快速组装、FAK和桩蛋白的酪氨酸磷酸化，以及随后DNA合成的增强。所有这些效应都需要细胞与ECM的黏附，并且当细胞接种在涂有多聚-L -赖氨酸或伴刀豆球蛋白A的底物上时不会发生。酪氨酸磷酸化抑制剂和细胞收缩性抑制剂也消除了微管破坏对黏附依赖性信号转导的影响。
结论：在附着于ECM的细胞中，微管破坏激活整合素依赖性信号级联，这导致基质黏附的组装和DNA合成的诱导。细胞收缩性的增加是这个信号过程中不可或缺的中间步骤。（C）当代生物学有限公司，国际标准连续出版物编号0960 - 9822
Background: The adhesion of cells to the extracellular matrix (ECM) generates transmembrane signals that affect cell proliferation, differentiation and survival. These signals are triggered by interactions between integrin and the ECM and involve tyrosine phosphorylation of specific proteins, including focal adhesion kinase (FAK) and paxillin, and the assembly of focal adhesions and actin bundles. In matrix-adherent, serum-starved Swiss 3T3 cells, the system of focal adhesions and actin bundles is poorly developed, and the level of tyrosine phosphorylation of FAK and paxillin is low. A number of growth factors rapidly stimulate tyrosine phosphorylation of these proteins and the assembly of focal adhesions and actin bundles. Growth factors and adhesion to the ECM are both necessary for the subsequent transition of cells to the S-phase of the cell cycle.Results: In serum-starved Swiss 3T3 cells, the disruption of microtubules by nocodazole or vinblastine, without the addition of external growth factors, induces the rapid assembly of focal adhesions and microfilament bundles, tyrosine phosphorylation of FAK and paxillin, and subsequent enhancement of DNA synthesis. All these effects require cell adhesion to the ECM and do not occur when cells are plated on substrates coated with poly-L-lysine or concanavalin A. Inhibitors of tyrosine phosphorylation and cell contractility also eliminate the effects of microtubule disruption on adhesion-dependent signal transduction.Conclusions: In ECM-attached cells, microtubule disruption activates the integrin-dependent signaling cascade, which leads to the assembly of matrix adhesions and the induction of DNA synthesis. The increase in cell contractility is an indispensable intermediate step in this signaling process. (C) Current Biology Ltd ISSN 0960-9822