Two EGF molecules contribute additively to stabilization of the EGFR dimer
Two EGF molecules contribute additively to stabilization of the EGFR dimer
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DOI：
10.1093/emboj/16.2.281
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发表时间：
1997-01-15
期刊：
影响因子：
11.4
通讯作者：
Schlessinger, J
中科院分区：
文献类型：
--
作者：
Lemmon, MA;Bu, ZM;Schlessinger, J
受体二聚化通常被认为是生长因子与其细胞表面受体结合后的主要信号传导事件，然而，除了对人生长激素（hGH）受体的研究外，对配体诱导的受体二聚化的精确分子细节知之甚少，我们用滴定量热法分析了表皮生长因子（EGF）与其受体胞外区（sEGFR）的结合，和使用小角X射线散射产生的sEGFR二聚化，EGF诱导含有两个EGF分子的sEGFR二聚体的定量形成。从这两种方法获得的数据表明一个EGF单体结合一个sEGFR单体的模型，受体二聚化涉及随后两个单体（1：1）EGF-sEGFR复合物的缔合。二聚化可能由二聚体中两个EGF分子的二价结合和/或受体-受体相互作用引起。对两个（可能是二价的）EGF单体的需要将EGF诱导的sEGFR二聚化与hGH和干扰素-γ受体区分开来，其中单个配体种类（单体或二聚体）的多价结合驱动受体寡聚化。EGF诱导的sEGFR二聚化的拟议模型表明EGFR（或erbB）受体家族的配体诱导的同源和异源二聚化的可能机制。
Receptor dimerization is generally considered to be the primary signaling event upon binding of a growth factor to its receptor at the cell surface, Little, however, is known about the precise molecular details of ligand-induced receptor dimerization, except for studies of the human growth hormone (hGH) receptor, We have analyzed the binding of epidermal growth factor (EGF) to the extracellular domain of its receptor (sEGFR) using titration calorimetry, and the resulting dimerization of sEGFR using small-angle X-ray scattering, EGF induces the quantitative formation of sEGFR dimers that contain two EGF molecules, The data obtained from the two approaches suggest a model in which one EGF monomer binds to one sEGFR monomer, and that receptor dimerization involves subsequent association of two monomeric (1:1) EGF-sEGFR complexes, Dimerization may result from bivalent binding of both EGF molecules in the dimer and/or receptor-receptor interactions, The requirement for two (possibly bivalent) EGF monomers distinguishes EGF-induced sEGFR dimerization from the hGH and interferon-gamma receptors, where multivalent binding of a single ligand species (either monomeric or dimeric) drives receptor oligomerization. The proposed model of EGF-induced sEGFR dimerization suggests possible mechanisms for both ligand-induced homo- and heterodimerization of the EGFR (or erbB) family of receptors.