Huynh-Do U, Stein E, Lane A A, Liu H, Cerretti D P, Daniel T O
Division of Nephrology, Departments of Medicine and Cell Biology, and the Vanderbilt Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232-2372, USA.
EMBO J. 1999 Apr 15;18(8):2165-73. doi: 10.1093/emboj/18.8.2165.
Receptors of the Eph family and their ligands (ephrins) mediate developmental vascular assembly and direct axonal guidance. Migrating cell processes identify appropriate targets within migratory fields based on topographically displayed ephrin gradients. Here, EphB1 regulated cell attachment by discriminating the density at which ephrin-B1 was displayed on a reconstituted surface. EphB1-ephrin-B1 engagement did not promote cell attachment through mechanical tethering, but did activate integrin-mediated attachment. In endothelial cells, attachment to RGD peptides or fibrinogen was mediated through alphavbeta3 integrin. EphB1 transfection conferred ephrin-B1-responsive activation of alpha5beta1 integrin-mediated cell attachment in human embryonic kidney cells. Activation-competent but signaling-defective EphB1 point mutants failed to stimulate ephrin-B1 dependent attachment. These findings lead us to propose that EphB1 functions as a 'ligand density sensor' to signal integrin-mediated cell-matrix attachment.
Eph家族受体及其配体（ephrins）介导发育过程中的血管组装并指导轴突导向。迁移的细胞突起根据地形显示的ephrin梯度在迁移区域内识别合适的靶点。在这里，EphB1通过区分重组表面上ephrin-B1的展示密度来调节细胞附着。EphB1与ephrin-B1的结合并非通过机械拴系促进细胞附着，而是激活整合素介导的附着。在内皮细胞中，与RGD肽或纤维蛋白原的附着是通过αvβ3整合素介导的。EphB1转染赋予人胚肾细胞中α5β1整合素介导的细胞附着对ephrin-B1的反应性激活。具有激活能力但信号缺陷的EphB1点突变体未能刺激ephrin-B1依赖性附着。这些发现使我们提出，EphB1作为一种“配体密度传感器”，为整合素介导的细胞-基质附着发出信号。
