Distinctive effects of the carboxyl-terminal sequence of the insulin-like growth factor I receptor on its signaling functions.
Distinctive effects of the carboxyl-terminal sequence of the insulin-like growth factor I receptor on its signaling functions.
复制标题
胰岛素样生长因子 I 受体的羧基末端序列对其信号传导功能的独特影响。
DOI：
10.1128/jvi.67.11.6835-6840.1993
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发表时间：
1993
影响因子：
5.4
通讯作者：
Wang,LH
中科院分区：
文献类型：
--
作者：
Liu,D;Zong,CS;Wang,LH
我们以前已经表明，人胰岛素受体（IR）和胰岛素样生长因子I受体（IGFR）的细胞外序列对蛋白酪氨酸激酶（PTK）活性和其各自的GAG受体融合蛋白的生物学功能具有抑制作用。为了研究IGFR羧基序列在调节Gag-IGFR PTK和生物学活性中的作用，从编码Gag-IGFR的亲本病毒UIGFR构建了分别含有17、27、47、67和88个氨基酸（aa）的羧基缺失的5个突变体CM 1、CM 2、CM 3、CM 4和CM 5。缺失27个氨基酸对UIGFR的细胞转化和PTK活性影响不大。CM 3中47个氨基酸的缺失使PTK和转化活性消失。令人惊讶的是，除了CM 3中的20个aa之外，CM 4中进一步缺失20个aa重新激活了激酶和转化活性。CM 5，含有20个氨基酸的删除超出CM 4，只有边际转化和PTK活动。我们得出结论，Gag-IGFR的羧基区域的缺失使其转化活性失活，而不是像Gag-IR的情况下那样激活，并且氨基酸序列1250至1310对于PTK和转化活性是必需的。对上述全长IGFR及其突变体受体与磷脂酰肌醇3激酶结合的能力的分析表明，这种结合需要受体的PTK活性和酪氨酸磷酸化，并与它们的转化活性密切相关。羧基88氨基酸对于缔合不是必需的。
We have shown previously that the extracellular sequences of the human insulin receptor (IR) and the insulin-like growth factor I receptor (IGFR) have an inhibitory effect on protein tyrosine kinase (PTK) activity and on the biological functions of their respective Gag-receptor fusion proteins. To study the role of IGFR carboxyl sequence in modulation of the Gag-IGFR PTK and biological activities, five mutants, CM1, CM2, CM3, CM4, and CM5, containing carboxyl deletions of 17, 27, 47, 67, and 88 amino acids (aa), respectively, were constructed from the parental virus UIGFR encoding the Gag-IGFR. Deletion of up to 27 aa had little effect on the cell-transforming and PTK activities of UIGFR. Deletions of 47 aa in CM3 abolished PTK and transforming activities. Surprisingly, a further deletion of 20 aa in CM4 beyond that in CM3 reactivated the kinase and transforming activities. CM5, containing a deletion of 20 aa beyond that in CM4, had only marginal transforming and PTK activities. We conclude that deletion of the carboxyl region of the Gag-IGFR inactivates, instead of activating as in the case with Gag-IR, its transforming activity and the amino acid sequence 1250 to 1310 is essential for PTK and transforming activities. Analysis of the ability of the full-length IGFR and its mutant receptors described above to associate with phosphatidylinositol 3 kinase indicated that the association required PTK activity and tyrosine phosphorylation of the receptors and correlated well with their transforming activities. The carboxyl 88 aa are not essential for the association.