SYNERGISTIC ROLES FOR RECEPTOR OCCUPANCY AND AGGREGATION IN INTEGRIN TRANSMEMBRANE FUNCTION
SYNERGISTIC ROLES FOR RECEPTOR OCCUPANCY AND AGGREGATION IN INTEGRIN TRANSMEMBRANE FUNCTION
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DOI：
10.1126/science.7846531
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发表时间：
1995-02-10
期刊：
影响因子：
56.9
通讯作者：
YAMADA, KM
中科院分区：
文献类型：
--
作者：
MIYAMOTO, S;AKIYAMA, SK;YAMADA, KM
整联蛋白受体介导细胞黏附、信号转导和细胞骨架组织。通过比较受体占位和聚集的作用，阐明了单个跨膜受体如何实现多种功能。单价配体对整联蛋白的占位诱导受体重新分布，但酪氨酸磷酸化信号或细胞骨架蛋白重新分布极少。非抑制性单克隆抗体使整联蛋白在微珠上聚集，诱导pp125（FAK）和张力蛋白在细胞内积聚以及磷酸化，但其他细胞骨架蛋白（如踝蛋白）没有积聚。将抗体介导的簇集与单价配体占位相结合，诱导了七种细胞骨架蛋白的积聚，包括α-辅肌动蛋白、踝蛋白和F - 肌动蛋白，从而模拟了与纤连蛋白或多价肽的多价相互作用。因此，整联蛋白通过受体聚集、受体占位或两者共同的不同作用介导一系列复杂的功能。
Integrin receptors mediate cell adhesion, signal transduction, and cytoskeletal organization. How a single transmembrane receptor can fulfill multiple functions was clarified by comparing roles of receptor occupancy and aggregation. Integrin occupancy by monovalent ligand induced receptor redistribution, but minimal tyrosine phosphorylation signaling or cytoskeletal protein redistribution. Aggregation of integrins by noninhibitory monoclonal antibodies on beads induced intracellular accumulations of pp125(FAK) and tensin, as well as phosphorylation, but no accumulation of other cytoskeletal proteins such as talin. Combining antibody-mediated clustering with monovalent ligand occupancy induced accumulation of seven cytoskeletal proteins, including alpha-actinin, talin, and F-actin, thereby mimicking multivalent interactions with fibronectin or polyvalent peptides. Integrins therefore mediate a complex repertoire of functions through the distinct effects of receptor aggregation, receptor occupancy, or both together.