Tartare S, Mothe I, Kowalski-Chauvel A, Breittmayer J P, Ballotti R, Van Obberghen E
Unité 145, Institut National de la Santé et de la Recherche Médicale, Faculté de Médecine, Nice, France.
J Biol Chem. 1994 Apr 15;269(15):11449-55.
Insulin-like growth factor-1 receptors (IGF-1R) and insulin receptors (IR) are closely related tyrosine kinases. However, the IR plays a major role in metabolism control, whereas the IGF-1R is mainly involved in growth and differentiation. With these observations in mind, we wished to define the regions of IR and IGF-1R responsible for generation of biological specificity. We constructed a chimeric IGF-1R in which the carboxyl-terminal domain was replaced by that of IR. This receptor (IGF/CTIR) was expressed in NIH3T3 cells, and we compared its biological activity with that of wild-type receptors. The IGF/CTIR was fully functional regarding kinase activity and biological properties. Comparison of insulin and IGF-1 effects on IR and IGF-1R cells, respectively, indicated that the IR is more efficient in stimulating glycogen synthesis and p44mapk activity than is the IGF-1R. Interestingly, in IGF/CTIR16 cells expressing only 250,000 receptors glycogen synthesis was better stimulated than in IGF-1R cells with 600,000 receptors. Similarly, p44mapk activation was slightly higher in IGF/CTIR16 cells than in IGF-1R cells. These results suggest that the carboxyl-terminal domain of IR is more tightly coupled to the stimulation of glycogen synthesis and to the p44mapk pathway than is that of IGF-1R. We propose that this domain plays a crucial role in the transmission of biological effects and could account, at least in part, for receptor specificity.
胰岛素样生长因子-1受体（IGF-1R）和胰岛素受体（IR）是密切相关的酪氨酸激酶。然而，IR在代谢控制中起主要作用，而IGF-1R主要参与生长和分化。基于这些观察结果，我们希望确定IR和IGF-1R中负责产生生物学特异性的区域。我们构建了一种嵌合IGF-1R，其中羧基末端结构域被IR的羧基末端结构域所取代。这种受体（IGF/CTIR）在NIH3T3细胞中表达，我们将其生物学活性与野生型受体的生物学活性进行了比较。IGF/CTIR在激酶活性和生物学特性方面具有完全功能。分别比较胰岛素和IGF-1对IR和IGF-1R细胞的作用，结果表明IR在刺激糖原合成和p44mapk活性方面比IGF-1R更有效。有趣的是，在仅表达250,000个受体的IGF/CTIR16细胞中，糖原合成比在具有600,000个受体的IGF-1R细胞中受到更好的刺激。同样，IGF/CTIR16细胞中p44mapk的激活略高于IGF-1R细胞。这些结果表明，IR的羧基末端结构域比IGF-1R的羧基末端结构域与糖原合成的刺激以及p44mapk途径的耦合更紧密。我们认为该结构域在生物学效应的传递中起关键作用，并且至少可以部分解释受体特异性。
