Miyamoto S, Akiyama S K, Yamada K M
Laboratory of Developmental Biology, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892-4370.
Science. 1995 Feb 10;267(5199):883-5. doi: 10.1126/science.7846531.
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 pp125FAK 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.
整合素受体介导细胞黏附、信号转导和细胞骨架组织。通过比较受体占据和聚集的作用，阐明了单个跨膜受体如何实现多种功能。单价配体占据整合素会诱导受体重新分布，但酪氨酸磷酸化信号传导或细胞骨架蛋白重新分布极少。珠子上的非抑制性单克隆抗体使整合素聚集会诱导pp125FAK和张力蛋白在细胞内积累以及磷酸化，但不会使其他细胞骨架蛋白（如踝蛋白）积累。将抗体介导的聚集与单价配体占据相结合会诱导包括α-辅肌动蛋白、踝蛋白和F-肌动蛋白在内的七种细胞骨架蛋白积累，从而模拟与纤连蛋白或多价肽的多价相互作用。因此，整合素通过受体聚集、受体占据或两者共同的不同作用介导一系列复杂的功能。
