Neurotensin receptor-1 and-3 complex modulates the cellular signaling of neurotensin in the HT29 cell line
Neurotensin receptor-1 and-3 complex modulates the cellular signaling of neurotensin in the HT29 cell line
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DOI：
10.1053/gast.2002.36000
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发表时间：
2002-10-01
期刊：
影响因子：
29.4
通讯作者：
Mazella, J
中科院分区：
文献类型：
--
作者：
Martin, S;Navarro, V;Mazella, J
背景与目的：神经降压素（neurotensin，NT）是一种神经肽，它通过与3种不同的受体相互作用而发挥其细胞内效应。其中两种受体（NTR 1和NTR 2）属于G蛋白偶联受体家族，而第三种受体（NTR 3）是具有单个跨膜结构域的1型受体。我们最近发现，2个结构不同的受体NTR 1和NTR 3共表达在几个人癌细胞上，NT发挥增殖作用。研究方法：在这里，通过免疫沉淀的方法，我们提供了一个内源性异源二聚体的G蛋白偶联受体NTR 1与NTR 3在人腺癌细胞系HT 29的生化证据。结果如下：我们表明，这两种受体的表达和共定位在HT 29细胞的细胞表面，它们已经相互作用，形成一个异二聚体。然后NTR 1-NTR 3复合物在NT刺激下内化。结论：这2个结构无关的NT受体之间形成的复合物调节NT诱导的促分裂原活化蛋白激酶磷酸化和NTR 1介导的磷酸肌醇（PI）周转。
Background & Aims: The neuropeptide neurotensin (NT) exerts its intracellular effect by interacting with 3 different receptors. Two of these receptors (NTR1 and NTR2) belong to the G protein-coupled receptor family, whereas the third one (NTR3) is a type 1 receptor with a single transmembrane domain. We recently showed that the 2 structurally different receptors NTR1 and NTR3 were coexpressed in several human cancer cells on which NT exerts proliferative effects. Methods: Here, by an immunoprecipitation approach, we provide biochemical evidence for an endogenous heterodimerization of the G protein-coupled receptor NTR1 with the NTR3 in the human adenocarcinoma cell line HT29. Results: We show that both receptors are expressed and colocalized within the cell surface of HT29 cells where they already interact to form a heterodimer. The NTR1-NTR3 complex is then internalized on NT stimulation. Conclusions: The complex formed between these 2 structurally unrelated NT receptors modulates both the NT-induced phosphorylation of mitogen-activated protein kinases and the phosphoinositide (PI) turnover mediated by the NTR1.