Ponzio G, Dolais-Kitabgi J, Louvard D, Gautier N, Rossi B
EMBO J. 1987 Feb;6(2):333-40. doi: 10.1002/j.1460-2075.1987.tb04759.x.
This paper describes the properties of rabbit polyclonal antibodies directed against purified human insulin receptor which strongly stimulate the intrinsic tyrosine kinase activity. The stimulatory effect of the antibodies on the kinase activity was obtained on the insulin receptor autophosphorylation as well as on the kinase activity towards a synthetic substrate. This stimulation is additive to that induced by insulin. Moreover, rabbit antibodies do not impair insulin binding. These data strongly suggest that antibodies and insulin act through separate pathways. This conclusion is reinforced by the differences observed on the phosphopeptide maps of the receptor's beta subunit whose phosphorylation was performed either in the presence of insulin or rabbit antibodies. Interestingly, these polyclonal antibodies can also induce an activation of the receptor autophosphorylation by interacting only with extracellular determinants. The anti-insulin receptor antibodies mimic insulin in their stimulatory effect on amino acid (AIB) uptake, but they have a different effect to that found on the kinase activity; the simultaneous addition of the antiserum and insulin failed to stimulate this amino acid transport over the level induced by a saturating concentration of hormone.
本文描述了针对纯化的人胰岛素受体的兔多克隆抗体的特性，这些抗体能强烈刺激内在酪氨酸激酶活性。抗体对激酶活性的刺激作用在胰岛素受体自身磷酸化以及对合成底物的激酶活性方面均有体现。这种刺激作用与胰岛素诱导的刺激作用相加。此外，兔抗体不损害胰岛素结合。这些数据有力地表明抗体和胰岛素通过不同途径发挥作用。在受体β亚基的磷酸肽图谱上观察到的差异进一步强化了这一结论，该磷酸化过程分别在胰岛素或兔抗体存在的情况下进行。有趣的是，这些多克隆抗体仅通过与细胞外决定簇相互作用就能诱导受体自身磷酸化的激活。抗胰岛素受体抗体在刺激氨基酸（AIB）摄取方面模拟胰岛素，但它们对激酶活性的影响不同；同时添加抗血清和胰岛素未能在饱和浓度激素诱导的水平之上刺激这种氨基酸转运。
