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Signal transduction mechanisms for the regulation of EGF receptor gene expression.

调节EGF受体基因表达的信号转导机制。

基本信息

批准号：
02670115
负责人：
GAMOU Shinobu
金额：
$ 1.47万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670115/
关键词：
EGF Receptor Protein kinase C Gene expression Inhibitor Phosphorylation 増殖因子情報伝達

项目摘要

1. Regulation of EGF receptor (EGFR) gene expression in a variant isolated from an EGFR-deficient small cell lung carcinoma (SCLC) cell line.Most cell lines derived from SCLC grow in an anchorage-independent manner ; they neither possess EGF binding activity nor express EGFR mRNA. A variant AD320, which grew In an anchorage-dependent manner with altered morphology, was isolated from SCLC cell line Lul34. EGFR mRNA and EGF binding activity could be detected In the varlant. Drastle change In gene expression Including a decrease of creatlne klnase B mRNA and an increase of c-mye mRNA were observed. The EGFR In the variant appeared to be an active part of the transmembrane signaling machinery since c-fos and c-jun mRNA accumulated after ISGF and a tumor promoter TPA treatment, followed by EGFR mRNA and c-myc mRNA accumulation. Thus, the Inducible regulatory mechanism for EGFR gene was activated in the variant even though the EGFR gene was constitutively expressed.2. Unique induction of EGF … More receptor phosphorylation and early-response gene expression by protein kinase C inhibitor Calpbostin-c.Calphostin-c is known to bind the regulatory domain of protein kinase C and t6 inhibit kinase activity in vitro in a light dependent fashion. We have found that calphostin-c induces unique cellular responses in a light dependent fashion when the EGF receptor hyperproducing squamous carcinoma cell line NA and the lung adenocareinoma cell line A549 were treated with tills compound. Phosphorylation of EGF receptor was observed 30 min after calphostln-c/llght treatment. Phosphoamino acid analysis revealed the receptor phosphorylation on serine and threonine residues. EGF binding activity was markedly reduced when treated under light, suggesting apparent internalization of the phosphorylated cell surface receptor. Furthermore, cal-c markedly enhoned e-fos and c-jun gene expression. These results suggest that calphostin-c induces a unique phosphorylation of EGF receptor and activate signal transduction pathway, which appears to be different from EGF- and TPA-activated pathways. Less

1.从EGFR缺陷型小细胞肺癌（SCLC）细胞系中分离的变异体中EGF受体（EGFR）基因表达的调节。大多数SCLC细胞系以锚定非依赖性方式生长;它们既不具有EGF结合活性，也不表达EGFR mRNA。从SCLC细胞系Lul 34中分离出以锚定依赖性方式生长并具有改变的形态的变体AD 320。在变异体中可检测到EGFR mRNA和EGF结合活性。基因表达的显著变化包括肌酸激酶B mRNA的减少和c-mye mRNA的增加。EGFR在变体中似乎是跨膜信号传导机制的活性部分，因为在ISGF和肿瘤促进剂TPA处理后c-fos和c-jun mRNA积累，随后是EGFR mRNA和c-myc mRNA积累。因此，即使EGFR基因是组成型表达的，EGFR基因的诱导型调控机制在变异体中也被激活. EGF的独特功效 ...更多信息通过蛋白激酶C抑制剂Calpbostin-c的受体磷酸化和早期反应基因表达。已知Calpbostin-c结合蛋白激酶C的调节结构域，并且t6以光依赖性方式在体外抑制激酶活性。我们发现，当用TILL化合物处理EGF受体高表达的鳞状细胞癌细胞系NA和肺腺癌细胞系A549时，钙蛋白-C以光依赖的方式诱导独特的细胞反应。在CalphostIn-c/光照处理后30分钟观察到EGF受体的磷酸化。磷酸化氨基酸分析揭示了丝氨酸和苏氨酸残基上的受体磷酸化。EGF结合活性显着降低时，在光下处理，表明明显的磷酸化细胞表面受体的内化。此外，cal-c还能显著增强e-fos和c-jun基因的表达。这些结果表明，calphostin-c诱导的EGF受体的磷酸化和激活的信号转导途径，这似乎是不同的EGF和TPA激活的途径。少