GROWTH-FACTORS AND MEMBRANE DEPOLARIZATION ACTIVATE DISTINCT PROGRAMS OF EARLY RESPONSE GENE-EXPRESSION - DISSOCIATION OF FOS AND JUN INDUCTION
GROWTH-FACTORS AND MEMBRANE DEPOLARIZATION ACTIVATE DISTINCT PROGRAMS OF EARLY RESPONSE GENE-EXPRESSION - DISSOCIATION OF FOS AND JUN INDUCTION
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DOI：
10.1101/gad.3.3.304
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发表时间：
1989-03-01
影响因子：
10.5
通讯作者：
GREENBERG, ME
中科院分区：
文献类型：
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作者：
BARTEL, DP;SHENG, M;GREENBERG, ME
已经鉴定了一组早期应答基因，其在成纤维细胞中的转录响应于生长因子而被快速诱导。该组的原型成员c-fos和c-jun编码形成异源二聚体的产物，并参与基因表达和细胞生长的调节。据认为，其他早期反应基因也编码细胞对外部刺激反应的关键介质。我们已经使用PC 12嗜铬细胞瘤细胞作为模型系统来测试的假设，不同的细胞外信号诱导不同的模式的早期反应基因的表达。我们的研究结果表明，膜去极化，诱导氯化钾或神经递质类似物尼古丁，激活一个程序的基因表达不同的神经生长因子或表皮生长因子激活。值得注意的是，c-fos和c-jun的激活可以分离，而c-jun与c-fos和jun-B在生长因子刺激后共同诱导，膜去极化激活c-fos和jun-B而不刺激c-jun。编码推定的转录因子的努尔/77和zif/268也显示出对生长因子和去极化的显著不同的反应。我们的结论是，多个非会聚信号转导途径控制早期反应基因的表达。我们的研究结果还表明，细胞对环境变化的反应的多样性和特异性可以解释为相对少量的早期反应基因的差异组合诱导。
A set of early response genes has been identified whose transcription in fibroblasts is rapidly induced in response to growth factors. Prototype members of this group, c-fos and c-jun, encode products that form a heterodimer and have been implicated in the regulation of gene expression and cell growth. It is thought that other early response genes also encode critical mediators of the cell''s response to external stimuli. We have used PC12 pheochromocytoma cells as a model system to test the hypothesis that different extracellular signals induce distinct patterns of expression of early response genes. Our results indicate that membrane depolarization, induced either by potassium chloride or by the neurotransmitter analog nicotine, activates a program of gene expression distinct from that activated by nerve growth factor or epidermal growth factor. Notably, c-fos and c-jun activation can be dissociated; whereas c-jun is coinduced with c-fos and jun-B after growth factor stimulation, membrane depolarization activates c-fos and jun-B without stimulating c-jun. Fos may therefore form transcription complexes with alternative cofactors under different stimulation conditions. nur/77 and zif/268, which encode putative transcription factors, also show markedly different responses to growth factors and depolarization. We conclude that multiple nonconvergent signal transduction pathways control early response gene expression. Our findings also indicate that the diversity and specificity of cellular response to environmental change can be accounted for by the differential combinatorial induction of a relatively small number of early response genes.