Sjaastad M D, Angres B, Lewis R S, Nelson W J
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, CA 94305-5426.
Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8214-8. doi: 10.1073/pnas.91.17.8214.
Integrin binding to extracellular matrix (ECM) regulates cell migration and gene expression in embryogenesis, metastasis, would healing, and the inflammatory response. In many cases, binding of integrins to ECM triggers intracellular signaling pathways. The regulatory roles of intracellular signaling mechanisms in these events are poorly understood. Using single-cell analysis, we demonstrate that beads coated with peptide containing Arg-Gly-Asp (RGD), an integrin recognition motif found in many ECM proteins, elicit a rapid transient increase in intracellular calcium in Madin-Darby canine kidney (MDCK) epithelial cells. Also, significantly more beads bind to responding cells than to nonresponders. Several independent methods that inhibit RGD-induced Ca2+ signaling decrease both the number of beads bound and the strength of adhesion to an RGD-coated substratum. These results indicate that intracellular Ca2+ signaling participates in a positive feedback loop that enhances integrin-mediated cell adhesion.
整合素与细胞外基质（ECM）的结合在胚胎发育、转移、伤口愈合和炎症反应中调节细胞迁移和基因表达。在许多情况下，整合素与ECM的结合会触发细胞内信号通路。细胞内信号机制在这些事件中的调节作用尚不清楚。通过单细胞分析，我们证明，包被有含精氨酸-甘氨酸-天冬氨酸（RGD）肽的珠子（RGD是在许多ECM蛋白中发现的整合素识别基序）可引起Madin-Darby犬肾（MDCK）上皮细胞内钙离子的快速短暂增加。此外，与无反应细胞相比，与有反应细胞结合的珠子明显更多。几种抑制RGD诱导的Ca2+信号传导的独立方法，既能减少结合的珠子数量，也能降低对RGD包被基质的粘附强度。这些结果表明，细胞内Ca2+信号传导参与了一个正反馈回路，该回路增强了整合素介导 的细胞粘附。
