Experimental approaches to hypothetical hormones: detection of a candidate ligand of the neu protooncogene.
Experimental approaches to hypothetical hormones: detection of a candidate ligand of the neu protooncogene.
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假设激素的实验方法：检测 neu 原癌基因的候选配体。
DOI：
10.1073/pnas.86.9.3179
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发表时间：
1989
影响因子：
11.1
通讯作者：
Weinberg,RA
中科院分区：
文献类型：
--
作者：
Yarden,Y;Weinberg,RA
编码跨膜酪氨酸激酶的癌基因越来越多，其结构类似于生长因子受体。在大多数情况下，这些假定受体的配体是未知的。使用新癌基因作为模型系统，我们开发了几种实验方法来检测此类假设的配体。以下证据共同表明，neu 编码的癌蛋白的候选配体是由 ras 转化的成纤维细胞分泌的： ras 转化体条件化的培养基能够诱导 neu 编码的 p185 下调，并在体外激活其内在酪氨酸激酶活性。此外，条件培养基诱导neu编码蛋白的酪氨酸残基体内磷酸化的快速增加。最后，将 neu 基因转移到造血细胞中，使它们对条件培养基产生有丝分裂反应。实验排除了通过其他已知受体，特别是表皮生长因子受体间接激活癌蛋白的可能性。
There is a growing list of oncogenes encoding transmembrane tyrosine kinases that have structures reminiscent of growth factor receptors. In most cases, the ligands for these putative receptors are unknown. Using the neu oncogene as a model system, we have developed several experimental approaches for the detection of such hypothetical ligands. The following lines of evidence collectively imply that a candidate ligand of the neu-encoded oncoprotein is secreted by ras-transformed fibroblasts: Medium conditioned by ras transformants is able to induce down-modulation of the neu-encoded p185 and to activate its intrinsic tyrosine kinase activity in vitro. In addition, a rapid increase in the phosphorylation in vivo of tyrosine residues of the neu-encoded protein is induced by the conditioned medium. Finally, transfer of the neu gene into hematopoietic cells renders them mitogenically responsive to the conditioned medium. The possibility of indirect activation of the oncoprotein through other known receptors, especially the receptor for the epidermal growth factor, was experimentally excluded.