[Leu 27 ] INSULIN-LIKE GROWTH FACTOR II IS HIGHLY SELECTIVE FOR THE TYPE-II IGF RECEPTOR IN BINDING, CROSS-LINKING AND THYMIDINE INCORPORATION EXPERIMENTS

作者：Margot W. Beukers, Youngman Oh, Heping Zhang, NICHOLAS C. LING, Ron G. Rosenfeld · 发表于：Endocrinology · 年份：1991 · DOI：10.1210/endo-128-2-1201 · 被引用次数：94 · 研究领域：Growth Hormone and Insulin-like Growth Factors、Metabolism, Diabetes, and Cancer、PI3K/AKT/mTOR signaling in cancer

Insulin-like growth factor-II (IGF-II) is able to interact with three different receptors: the type-I and type-II IGF receptors, and the insulin receptor, although with a lower affinity. This cross reactivity obscures the mechanisms via which the biological activities of IGF-II are mediated. We have synthesized an IGF-II analog, [Leu27]IGF-II, that is highly selective for the type-II IGF receptor. Receptor binding experiments demonstrate a high affinity for the type-II IGF receptor, analogous to synthetic (syn) and recombinant (rec) IGF-II, but no affinity for the type-I IGF and the insulin receptor at concentrations up to 50 and 200 ng/ml, respectively. The lack of affinity for these two receptors is confirmed by biological studies which demonstrated that this analog, in contrast with synIGF-II, did not stimulate [3H]thymidine incorporation in Balb/c 3T3 cells. [Leu27]IGF-II opens new ways to identify which actions of IGF-II are mediated via the type-II receptor and which are due to cross reactivity with the type-I IGF or the insulin receptor.