Blechman J M, Lev S, Barg J, Eisenstein M, Vaks B, Vogel Z, Givol D, Yarden Y
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Cell. 1995 Jan 13;80(1):103-13. doi: 10.1016/0092-8674(95)90455-7.
Receptor dimerization is ubiquitous to the action of all receptor tyrosine kinases, and in the case of dimeric ligands, such as the stem cell factor (SCF), it was attributed to ligand bivalency. However, by using a dimerization-inhibitory monoclonal antibody to the SCF receptor, we confined a putative dimerization site to the nonstandard fourth immunoglobulin-like domain of the receptor. Deletion of this domain not only abolished ligand-induced dimerization and completely inhibited signal transduction, but also provided insights into the mechanism of the coupling of ligand binding to dimer formation. These results identify an intrinsic receptor dimerization site and suggest that similar sites may exist in other receptors.
受体二聚化是所有受体酪氨酸激酶作用所共有的现象，对于二聚体配体，如干细胞因子（SCF）而言，其作用归因于配体的双价性。然而，通过使用针对SCF受体的二聚化抑制性单克隆抗体，我们将一个假定的二聚化位点定位到受体的非标准第四免疫球蛋白样结构域。缺失该结构域不仅消除了配体诱导的二聚化并完全抑制信号转导，还为配体结合与二聚体形成的偶联机制提供了见解。这些结果确定了一个内在的受体二聚化位点，并表明其他受体中可能存在类似位点。
