Miura M, Surmacz E, Burgaud J L, Baserga R
Jefferson Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
J Biol Chem. 1995 Sep 22;270(38):22639-44. doi: 10.1074/jbc.270.38.22639.
The wild type insulin-like growth factor I (IGF-I) receptor has both mitogenic and transforming activities. We have examined the effect of point mutations at tyrosine residues 1250 and 1251 on these two properties of the receptor. For this purpose, we stably transfected plasmids expressing mutant and wild type receptors into R- cells, which are 3T3-like cells, derived from mouse embryos with a targeted disruption of the IGF-I receptor genes, and therefore devoid of endogenous IGF-I receptors. A tyrosine to phenylalanine mutation of either the 1250 or 1251 residue, or both, has no effect on the ability of the receptor to transmit a mitogenic signal. However, the tyrosine 1251 mutant receptor and the double mutant have lost the ability to transform R- cells (colony formation in soft agar), even when the receptors are expressed at very high levels, while the Y1250F mutant is fully transforming. These experiments show that the 1251 tyrosine residue is required for the transforming activity of the IGF-I receptor.
野生型胰岛素样生长因子I（IGF-I）受体具有促有丝分裂和转化活性。我们研究了酪氨酸残基1250和1251处的点突变对该受体这两种特性的影响。为此，我们将表达突变型和野生型受体的质粒稳定转染到R-细胞中，R-细胞是类似3T3的细胞，源自具有IGF-I受体基因靶向破坏的小鼠胚胎，因此缺乏内源性IGF-I受体。1250或1251残基或两者的酪氨酸到苯丙氨酸突变对受体传递促有丝分裂信号的能力没有影响。然而，酪氨酸1251突变型受体和双突变体已经失去了转化R-细胞的能力（在软琼脂中形成集落），即使受体以非常高的水平表达，而Y1250F突变体具有完全转化能力。这些实验表明，1251酪氨酸残基是IGF-I受体转化活性所必需的。
