IDENTIFICATION OF A PHORBOL ESTER-REPRESSIBLE V-SRC-INDUCIBLE GENE
IDENTIFICATION OF A PHORBOL ESTER-REPRESSIBLE V-SRC-INDUCIBLE GENE
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DOI：
10.1073/pnas.86.4.1178
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发表时间：
1989-02-01
影响因子：
11.1
通讯作者：
ERIKSON, RL
中科院分区：
文献类型：
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作者：
SIMMONS, DL;LEVY, DB;ERIKSON, RL
感染温度敏感的Rous肉瘤病毒（RSV）突变体tsNY72-4的鸡胚成纤维细胞（CEF）在转移到允许温度后不久表达一组pp60v-src诱导的rna。通过差法和差法筛选，我们克隆了12个这样的序列，其中2个是c-fos和kox -24。血清诱导了所有的v-src诱导基因，这表明这些基因在正常细胞分裂中起作用，而不是特异性的转化本身。然而，值得注意的是，与血清相比，v-src产生了长时间的，在某些情况下动力学复杂的诱导模式。在大多数克隆中，phorbol 12-十四酸酯13-乙酸酯（TPA）诱导mrna的动力学与血清相似。然而，一个克隆（CEF-4）以双相方式表达。另一个mRNA （CEF-10）在1小时被TPA抑制，之后永久诱导。CEF-10 mRNA的抑制-诱导模式与细胞中蛋白激酶C （PKC）活性相反，表明PKC积极抑制该基因。体内CEF-10 mRNA的表达主要局限于肺。全长CEF-10 cDNA编码一个41 kda的蛋白，该蛋白具有一个供分泌的氨基末端信号肽，含有大量的半胱氨酸残基，与已知蛋白序列无相似性。
Chicken embryo fibroblasts (CEF) infected with a temperature-sensitive Rous sarcoma virus (RSV) mutant, tsNY72-4, express a set of pp60v-src-induced RNAs soon after shift to the permissive temperature. By subtractive and differential screening, we have cloned 12 of these sequences, 2 of which were c-fos and krox-24. Serum induced all the v-src inducible genes tested suggesting that these genes serve roles in normal cell division and are not specific to transformation per se. Significantly, however, v-src produced prolonged, and in some cases kinetically complex, patterns of induction compared to serum. For most of the clones, phorbol 12-tetradecanoate 13-acetate (TPA) induced mRNAs with kinetics similar to that of serum. However, one clone (CEF-4) was expressed in a biphasic manner. Another (CEF-10) was repressed by TPA at 1 hr, after which this mRNA was permanently induced. The pattern of repression-induction of CEF-10 mRNA is the inverse of protein kinase C (PKC) activity in the cell, suggesting that PKC actively represses this gene. In vivo expression of CEF-10 mRNA is restricted predominantly to the lung. A full-length CEF-10 cDNA encodes a 41-kDa protein that has an amino-terminal signal peptide for secretion, contains a markedly high number of cysteine residues, and shows no sequence similarity to known proteins.