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Role of the ERK MAP Kinase Cascade in the Regulation of Cell Proliferation and Differentiation.

ERK MAP 激酶级联在细胞增殖和分化调节中的作用。

基本信息

批准号：
08457613
负责人：
KOHNO Michiaki
金额：
$ 4.93万
依托单位：
Nagasaki University (1997)Gifu Pharmaceutical University (1996)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457613/
关键词：
Cell Growth Control Cell Differentiation ERK MAP kinases Hepatocyte Growth Factor Nerve Growth Factor Bone Morphogenetic Protein TGF-beta Superfamily p38 MAP kinase 増殖因子分化因子 MAPキナーゼ核移行転写因子細胞骨格骨形成因子

项目摘要

(1) Mitogen-activated protein (MAP) kinases play a pivotal role in the mitogenic signal transduction pathway and are essential components of the MAP kinase cascade, . In growth-arrested Swiss 3T3 cells, MAP kinases are mainly cytoplasmic. Subsequent to mitogenic stimulation by serum, MAP kinases are activated and translocated into nucleus. This translocation is rapid (seen in 10 min), persistent (up to 6 h), reversible (by removal of stimulus) and apparently coupled to the mitogenic potential.(2) HGF and PMA markedly induced the spreading, dissociation and scattering of MDCK cells. In all these agent-stimulated cells, rapid activation of Raf-1, MAP kinase/ERK kinase (MEK), 41-/43-kDa MAP kinases and p90^<rsk> was commonly observed. Pretreatment of MDCK cells with PD98059, a specific inhibitor of MEK,selectively inhibited the HGF- and PMA--stimulated activities of MEK,41-/43-kDa MAP kinases and p90r^<sk> in a dose dependent manner. Importantly, HGF- and PMA-induced scattering of MDCK ce … More lls was inhibited at doses of AMPC similar to those that gave comparable levels of inhibition of the activities of MEK,41-/43-kDa MAP kinases and p90^<rsk>. These results suggest that activation of the 41-/43-kDa MAP kinase signaling pathway is required for the motility response of MDCKcells induced by agents such as HGF and PMA.(3) BMP-2 induced morphological changes in PC12 cells with the concomitant expression of three neurofilament proteins. Unlike NGF and bFGF however, BMP-2 failed to induce the activation of either 41- and 43-kDa MAP kinases or the (MEK.Also, BMP-2 did not induce the expression of the c-fos gene in PC12 cells. Activin A was also capable of inducing the neuronal differentiation of PC12 cells without activating MAP kinases and MEK.These findings show a clear dissociation between the requirement for the activation of the MAP kinase cascade and the ability of BMP-2 and activin A to induce PC12 cell neuronal differentiation. In addition, these results suggest that the activation of MAP kinases and MEK is not an absolute requirement for PC12 cell differentiation. Less

(1)有丝分裂原活化蛋白（MAP）激酶在有丝分裂信号转导通路中起关键作用，是MAP激酶级联反应的重要组成部分。在生长停滞的Swiss 3 T3细胞中，MAP激酶主要在细胞质中。在血清促有丝分裂刺激之后，MAP激酶被激活并移位到细胞核中。这种易位是快速的（在10分钟内观察到），持久的（长达6小时），可逆的（通过去除刺激），并显然耦合到促有丝分裂的潜力。(2)HGF和PMA可明显诱导MDCK细胞的铺展、解离和离散。在所有这些试剂刺激的细胞中，通常观察到Raf-1、MAP激酶/ERK激酶（MEK）、41-/43-kDa MAP激酶和p90 β的快速活化<rsk>。用MEK的特异性抑制剂PD 98059预处理MDCK细胞，以剂量依赖方式选择性地抑制HGF和PMA刺激的MEK、41-/43-kDa MAP激酶和p90激酶的活性<sk>。重要的是，HGF和PMA诱导的MDCK细胞的散射， ...更多信息在AMPC的剂量下，Ils被抑制，其类似于对MEK、41-/43-kDa MAP激酶和p90 β的活性产生相当水平的抑制的剂量<rsk>。这些结果表明，41-/43-kDa MAP激酶信号通路的激活是必需的MDCK细胞的运动性反应的药物，如HGF和PMA诱导。(3)BMP-2诱导PC 12细胞的形态学变化，伴随着三种神经丝蛋白的表达。然而，与NGF和bFGF不同，BMP-2不能诱导41-和43-kDa MAP激酶或β-MEK的活化。BMP-2也不能诱导PC 12细胞中c-fos基因的表达。激活素A也能诱导PC 12细胞向神经元分化，但不激活MAP激酶和MEK。这些结果表明，激活MAP激酶级联反应的需要与BMP-2和激活素A诱导PC 12细胞向神经元分化的能力之间存在明显的分离。此外，这些结果表明，MAP激酶和MEK的激活不是PC 12细胞分化的绝对要求。少