RGD-independent binding of integrin alpha9beta1 to the ADAM-12 and -15 disintegrin domains mediates cell-cell interaction.
RGD-independent binding of integrin alpha9beta1 to the ADAM-12 and -15 disintegrin domains mediates cell-cell interaction.
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发表时间：
2000
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通讯作者：
K. Eto;W. Puzon‐McLaughlin;D. Sheppard;A. Sehara-Fujisawa;X. P. Zhang;Y. Takada
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作者：
K. Eto;W. Puzon‐McLaughlin;D. Sheppard;A. Sehara-Fujisawa;X. P. Zhang;Y. Takada
亚当斯（一种去整合素和金属蛋白酶）介导几个重要过程（例如肿瘤坏死因子-α释放、受精和成肌细胞融合）。ADAM去整合素结构域通常缺乏RGD基序，并且它们的受体实际上是未知的。在这里，我们表明，整合素α（9）β（1）特异性相互作用的重组亚当斯-12和-15去整合素结构域在一个RGD-独立的方式。我们还表明，ADAM-12或-15和alpha（9）beta（1）之间的相互作用支持细胞间相互作用。有趣的是，α（9）β（1）/ADAM介导的细胞粘附和细胞间相互作用所需的阳离子需求和整合素活化状态与已知的整合素-细胞外基质相互作用所需的相似。这些结果与最近报道的精子/卵子融合过程中ADAM-2/α（6）β（1）相互作用需要与细胞外基质相互作用不同的整合素活化状态完全不同。这些结果表明，α（9）β（1）可能是缺乏RGD基序的亚当斯的主要受体，考虑到亚当斯和α（9）β（1）的广泛分布，这种相互作用可能具有潜在的生物学和病理学意义。
ADAMs (a disintegrin and metalloproteases) mediate several important processes (e.g. tumor necrosis factor-alpha release, fertilization, and myoblast fusion). The ADAM disintegrin domains generally lack RGD motifs, and their receptors are virtually unknown. Here we show that integrin alpha(9)beta(1) specifically interacts with the recombinant ADAMs-12 and -15 disintegrin domains in an RGD-independent manner. We also show that interaction between ADAM-12 or -15 and alpha(9)beta(1) supports cell-cell interaction. Interestingly, the cation requirement and integrin activation status required for alpha(9)beta(1)/ADAM-mediated cell adhesion and cell-cell interaction is similar to those required for known integrin-extracellular matrix interaction. These results are quite different from recent reports that ADAM-2/alpha(6)beta(1) interaction during sperm/egg fusion requires an integrin activation status distinct from that for extracellular matrix interaction. These results suggest that alpha(9)beta(1) may be a major receptor for ADAMs that lack RGD motifs, and that, considering a wide distribution of ADAMs and alpha(9)beta(1), this interaction may be of potential biological and pathological significance.