Mitogen-activated protein kinase activation resulting from selective oncogene expression in NIH 3T3 and rat 1a cells.
Mitogen-activated protein kinase activation resulting from selective oncogene expression in NIH 3T3 and rat 1a cells.
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NIH 3T3 和大鼠 1a 细胞中选择性癌基因表达导致丝裂原激活蛋白激酶激活。
DOI：
10.1073/pnas.89.16.7355
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发表时间：
1992
影响因子：
11.1
通讯作者：
Johnson,GL
中科院分区：
文献类型：
--
作者：
Gallego,C;Gupta,SK;Heasley,LE;Qian,NX;Johnson,GL
丝裂原活化蛋白激酶（MAPK）是丝氨酸/苏氨酸激酶，其在许多细胞类型中响应于多种生长因子而快速活化。MAPK被酪氨酸和苏氨酸残基的磷酸化激活。它们被认为是生长因子受体转导系统的关键整合子，该系统涉及酪氨酸激酶信号转化为丝氨酸/苏氨酸激酶激活。我们研究了特定癌基因对NIH 3T3和大鼠1a成纤维细胞MAPK活性调节的影响。在NIH 3T3细胞中，ras或raf癌基因的表达，而不是gip2癌基因的表达，诱导一个显着的组成性MAPK激活。相反，在大鼠1a细胞中，gip 2，而不是ras或raf癌基因表达，诱导了强的组成性MAPK激活。这些发现表明，在细胞类型选择性的方式，不同的癌蛋白能够引起MAPK的组成性激活。然而，癌基因诱导的MAPK激活的幅度与任一细胞类型中的细胞转化没有直接相关性。在特定的细胞类型中，似乎只有转化癌基因的一个子集的表达能够改变MAPK活化途径的调节。因此，当相同的癌基因在不同的细胞类型中表达时，细胞质丝氨酸/苏氨酸激酶的网络将受到差异调节。
Mitogen-activated protein kinases (MAPKs) are serine/threonine kinases that are rapidly activated in response to a variety of growth factors in many cell types. MAPKs are activated by phosphorylation of both tyrosine and threonine residues. They are proposed to be key integrators of growth factor receptor transduction systems involving conversion of tyrosine kinase signals to serine/threonine kinase activation. We have studied the influence of specific oncogenes on the regulation of MAPK activity in NIH 3T3 and Rat 1a fibroblasts. In NIH 3T3 cells, ras or raf oncogene expression, but not gip2 oncogene expression, induces a significant constitutive MAPK activation. In contrast, in Rat 1a cells, gip2, but not ras or raf oncogene expression, induces a strong constitutive MAPK activation. The findings indicate that, in a cell type-selective manner, different oncoproteins are capable of causing the constitutive activation of MAPK. However, the magnitude of oncogene-induced MAPK activation is not directly correlated with cellular transformation in either cell type. It appears that expression of only a subset of transforming oncogenes in a specific cell type is able to alter the regulation of the MAPK activation pathway. Thus, the network of cytoplasmic serine/threonine kinases will be differentially regulated when the same oncogene is expressed in different cell types.