EGF RECEPTOR AND ERBB-2 TYROSINE KINASE DOMAINS CONFER CELL SPECIFICITY FOR MITOGENIC SIGNALING
EGF RECEPTOR AND ERBB-2 TYROSINE KINASE DOMAINS CONFER CELL SPECIFICITY FOR MITOGENIC SIGNALING
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DOI：
10.1126/science.2181668
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发表时间：
1990-04-06
期刊：
影响因子：
56.9
通讯作者：
PIERCE, JH
中科院分区：
文献类型：
--
作者：
DIFIORE, PP;SEGATTO, O;PIERCE, JH
表皮生长因子（EGF）受体（EGFR）转染白细胞介素-3（IL-3）依赖的32 D造血细胞后，可有效地与促有丝分裂信号通路偶联。当将与EGFR结构相关的表达载体forerbB-2或其截短的对应物ΔNerbB-2引入32 D细胞时，两者都不能诱导增殖。尽管其产物的过表达和组成型酪氨酸激酶活性处于与成纤维细胞靶细胞的有效转化相关的水平。因此，EGFR和derbB-2与不同的促有丝分裂信号通路偶联。负责细胞内信号转导特异性的区域定位于包含其各自酪氨酸激酶结构域的270个氨基酸的延伸。因此，生长因子受体信号传导的组织或细胞特异性调节可以在生长因子与受体的初始相互作用之后的某个点发生。这种信号传导的特异性可能是某些恶性肿瘤中某些癌基因选择性表达的原因。
The epidermal growth factor (EGF) receptor (EGFR) can efficiently couple with mitogenic signaling pathways when it is transfected into interleukin-3 (IL-3)-dependent 32D hematopoietic cells. When expression vectors forerbB-2, which is structurally related to EGFR, or its truncated counterpart, ΔNerbB-2, were introduced into 32D cells, neither was capable of inducing proliferation. This was despite overexpression and constitutive tyrosine kinase activity of their products at levels associated with potent transformation of fibroblast target cells. Thus, EGFR anderbB-2 couple with distinct mitogenic signaling pathways. The region responsible for the specificity of intracellular signal transduction was localized to a 270-amino acid stretch encompassing their respective tyrosine kinase domains. Thus, tissue- or cell-specific regulation of growth factor receptor signaling can occur at a point after the initial interaction of growth factor with receptor. Such specificity in signal transduction may account for the selection of certain oncogenes in some malignancies.