Morgan D O, Ho L, Korn L J, Roth R A
Proc Natl Acad Sci U S A. 1986 Jan;83(2):328-32. doi: 10.1073/pnas.83.2.328.
Thirty-six monoclonal antibodies to the human insulin receptor were produced. Thirty-four bound the intracellular domain of the receptor beta subunit, the domain containing the tyrosine-specific kinase activity. Of these 34 antibodies, 33 recognized the rat receptor and 1 was shown to precipitate the receptors from mice, chickens, and frogs with high affinity. Another of the antibodies inhibited the kinase activities of the human and frog receptors with equal potencies. This antibody inhibited the kinase activities of these receptors by more than 90%, whereas others had no effect on either kinase activity. Microinjection of the inhibiting antibody into Xenopus oocytes blocked the ability of insulin to stimulate oocyte maturation. In contrast, this inhibiting antibody did not block the ability of progesterone to stimulate the same response. Furthermore, control immunoglobulin and a noninhibiting antibody to the receptor beta subunit did not block this response to insulin. These results strongly support a role for the tyrosine-specific kinase activity of the insulin receptor in mediating this biological effect of insulin.
制备了36种针对人胰岛素受体的单克隆抗体。其中34种与受体β亚基的细胞内结构域结合，该结构域含有酪氨酸特异性激酶活性。在这34种抗体中，33种能识别大鼠受体，1种被证明能以高亲和力从小鼠、鸡和青蛙中沉淀出受体。另一种抗体以相同效力抑制人和青蛙受体的激酶活性。该抗体抑制这些受体的激酶活性超过90%，而其他抗体对两种激酶活性均无影响。将抑制性抗体显微注射到非洲爪蟾卵母细胞中可阻断胰岛素刺激卵母细胞成熟的能力。相比之下，这种抑制性抗体并不阻断孕酮刺激相同反应的能力。此外，对照免疫球蛋白和针对受体β亚基的非抑制性抗体并不阻断对胰岛素的这种反应。这些结果有力地支持了胰岛素受体的酪氨酸特异性激酶活性在介导胰岛素的这种生物学效应中所起的作用。
