Integrin-dependent activation of MAP kinase: a link to shape-dependent cell proliferation.
Integrin-dependent activation of MAP kinase: a link to shape-dependent cell proliferation.
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DOI：
10.1091/mbc.6.3.273
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发表时间：
1995-03
影响因子：
3.3
通讯作者：
Xiaoyun Zhu;R. Assoian
中科院分区：
文献类型：
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作者：
Xiaoyun Zhu;R. Assoian
细胞外基质粘附介导G1中后期细胞周期进程；这种效应涉及到细胞骨架的整合素依赖组织和随之而来的细胞形状的变化。为了确定与整合素依赖性形状变化相关的潜在信号转导因子，我们寻找了g0同步的NIH-3T3细胞长期粘附在纤维连接蛋白包被的培养皿上所刺激的激酶活性。这一过程刺激了几种激酶的活性，其中两种激酶在42和44 kDa时迁移，并在体外磷酸化髓鞘碱性蛋白。用抗磷酸酪氨酸和抗丝裂原活化蛋白（MAP）激酶抗体进行印迹检测，鉴定出这些酶为erk1和erk2。与血小板源性生长因子对这些MAP激酶的快速和短暂激活相反，纤连蛋白对MAP激酶活性的刺激是渐进的、持续的，并且与细胞扩散而不是细胞附着本身有关。细胞松弛素D阻断了由细胞与纤维连接蛋白结合引起的MAP激酶活性的激活。此外，MAP激酶也被细胞粘附于玻璃体粘连蛋白和IV型胶原活化；这些影响也与细胞扩散有关。这些结果区分了可溶性丝裂原和细胞外基质对G1期MAP激酶活性的调节。它们还涉及MAP激酶在形状依赖性细胞周期进程中的作用。
Adhesion to extracellular matrix mediates cell cycle progression in mid-late G1; this effect involves an integrin-dependent organization of the cytoskeleton and a consequent change in cell shape. In an effort to identify potential signal-transducing agents that are associated with integrin-dependent shape changes, we looked for kinase activities that were stimulated by long-term adhesion of G0-synchronized NIH-3T3 cells to fibronectin-coated dishes. Several kinase activities were stimulated by this procedure, two of which migrated at 42 and 44 kDa and phosphorylated myelin basic protein in vitro. Blotting with anti-phosphotyrosine and anti-mitogen-activated protein (MAP) kinase antibodies identified these enzymes as ERK 1 and ERK 2. In contrast to the rapid and transient activation of these MAP kinases by platelet-derived growth factor, stimulation of MAP kinase activity by fibronectin was gradual, persistent, and associated with cell spreading rather than cell attachment itself. Cytochalasin D blocked the activation of MAP kinase activity that was induced by the binding of cells to fibronectin. Moreover, MAP kinase was also activated by adhesion of cells to vitronectin and type IV collagen; these effects were also associated with cell spreading. These results distinguish the regulation of G1 phase MAP kinase activity by soluble mitogens and extracellular matrix. They also implicate MAP kinase in shape-dependent cell cycle progression.