由国际分子专家组成的科研小组发现了一个细胞信息交流的新机制。这项关于细胞行为的新发现或能有助于开发新的药物用于对抗癌症，风湿性关节炎和老年痴呆症等。
人解整合素样金属蛋白酶10（ADAM10），其竞争对象形状的改变将开启细胞交流过程。ADAM10能够分解蛋白，由于其重要的分子机制所以改变可能会引起严重的疾病。此外，细胞间的交流过程形成了某些疾病发展的基础。这项发现将改变我们对细胞行为的理解以及治疗药物的设计思路。Lackmann副教授介绍说。
这项关于细胞交流过程的发现相比于先前的观点更易于理解，并将会深刻影响未来生物医学研究的方向。
在实验中，研究人员发现，实际上，信号交流系统比复杂的信号通路更加直接和简单。他们表示，该过程是这样的：首先竞争细胞表面受体的形状发生改变，然后激活ADAM10蛋白酶传递变化并对相邻细胞产生影响。这其实是一个短暂的过程。
该研究结果发布在PLoS Biology的在线版本上。（生物谷Bioon.com）
生物谷推荐原始出处：
PLoS Biol 7(10): e1000215. doi:10.1371/journal.pbio.1000215
Cytoplasmic Relaxation of Active Eph Controls Ephrin Shedding by ADAM10
Peter W. Janes1#, Sabine H. Wimmer-Kleikamp1,2,3#¤, Achilleas S. Frangakis2, Kane Treble1, Bettina Griesshaber1, Ola Sabet3, Markus Grabenbauer3, Alice Y. Ting4, Paul Saftig5, Philippe I. Bastiaens2,3*, Martin Lackmann1*
1 Department of Biochemistry and Molecular Biology, Monash University, Victoria, Australia, 2 European Molecular Biology Laboratory, Heidelberg, Germany, 3 Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany, 4 Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America, 5 Biochemical Institute, Christian-Albrecht-University, Kiel, Germany
Release of cell surface-bound ligands by A-Disintegrin-And-Metalloprotease (ADAM) transmembrane metalloproteases is essential for signalling by cytokine, cell adhesion, and tyrosine kinase receptors. For Eph receptor ligands, it provides the switch between cell-cell adhesion and repulsion. Ligand shedding is tightly controlled by intrinsic tyrosine kinase activity, which for Eph receptors relies on the release of an inhibitory interaction of the cytoplasmic juxtamembrane segment with the kinase domain. However, a mechanism linking kinase and sheddase activities had remained elusive. We demonstrate that it is a membrane-proximal localisation of the latent kinase domain that prevents ephrin ligand shedding in trans. Fluorescence lifetime imaging microscopy and electron tomography reveal that activation extends the Eph receptor tyrosine kinase intracellular domain away from the cell membrane into a conformation that facilitates productive association with ADAM10. Accordingly, EphA3 mutants with constitutively-released kinase domains efficiently support shedding, even when their kinase is disabled. Our data suggest that this phosphorylation-activated conformational switch of EphA3 directly controls ADAM-mediated shedding.
