Receptor binding competition: A paradigm for regulating TGF-β family action.
Receptor binding competition: A paradigm for regulating TGF-β family action.
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DOI：
10.1016/j.cytogfr.2020.09.003
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发表时间：
2021-03
影响因子：
13
通讯作者：
Holien T
中科院分区：
文献类型：
--
作者：
Martinez-Hackert E;Sundan A;Holien T
转化生长因子（TGF）-β家族是一组结构相关的多功能生长因子或配体，其在动物组织的发育、调节和维持中至关重要。在人类中，家庭成员超过33人。这些分泌的配体通常与两种I型和两种II型受体形成多聚体复合物，以激活两个不同的信号转导分支之一。家庭的一个显著特点是滥交，即，许多配体结合相同的受体，并相互竞争结合这些受体。虽然对这一特征的几种解释已经被考虑过，但其功能意义仍然令人困惑。然而，最近的一些报道已经提出了这样的观点，即配体-受体结合混杂和竞争是TGF-β家族的关键特征，其提供了必要的调节功能。也就是说，它们允许细胞读取和处理多配体输入。这种能力可能是必要的，以产生微妙的，独特的，或适应性的反应，并可能促进发展的可塑性。在这里，我们回顾了配体竞争的分子基础，重点是分子结构和结合亲和力。我们给出了一个概述的方法，用于建立实验配体竞争。最后，我们讨论了如何配体竞争的概念可能从根本上与人类生理，疾病和治疗。
The transforming growth factor (TGF)-β family is a group of structurally related, multifunctional growth factors, or ligands that are crucially involved in the development, regulation, and maintenance of animal tissues. In humans, the family counts over 33 members. These secreted ligands typically form multimeric complexes with two type I and two type II receptors to activate one of two distinct signal transduction branches. A striking feature of the family is its promiscuity, i.e., many ligands bind the same receptors and compete with each other for binding to these receptors. Although several explanations for this feature have been considered, its functional significance has remained puzzling. However, several recent reports have promoted the idea that ligand-receptor binding promiscuity and competition are critical features of the TGF-β family that provide an essential regulating function. Namely, they allow a cell to read and process multi-ligand inputs. This capability may be necessary for producing subtle, distinctive, or adaptive responses and, possibly, for facilitating developmental plasticity. Here, we review the molecular basis for ligand competition, with emphasis on molecular structures and binding affinities. We give an overview of methods that were used to establish experimentally ligand competition. Finally, we discuss how the concept of ligand competition may be fundamentally tied to human physiology, disease, and therapy.
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