Hu Jiancheng, Strauch Pamela, Rubtsov Anatoly, Donovan Erin E, Pelanda Roberta, Torres Raul M
Integrated Department of Immunology, University of Colorado Health Sciences Center and National Jewish Medical and Research Center, Denver, CO 80206, USA.
Mol Immunol. 2008 Apr;45(7):1825-36. doi: 10.1016/j.molimm.2007.11.002. Epub 2007 Dec 21.
Lsc is a hematopoietic-restricted protein that functions as an effector of G alpha(12/13)-associated G-protein coupled receptors that activates RhoA. In the absence of Lsc leukocytes exhibit impaired migration and B lymphocytes inefficiently resolve integrin-mediated adhesion. Here, we demonstrate that Lsc exists physiologically in primary B lymphocytes as a large molecular weight complex resembling a homo-tetramer. Interfering with the assembly of this large molecular weight Lsc oligomer results in the activation of both Lsc functional activities and leads to cell rounding and inhibition of integrin-mediated adhesion. During cell migration on integrin ligands we find Lsc localizes predominantly toward the rear of migrating cells where we suggest it activates RhoA to resolve integin-mediated adhesion. Together these data demonstrate that Lsc regulates integrin-mediated adhesive events at the trailing edge of migrating cells.
Lsc是一种造血限制蛋白，作为与Gα(12/13)相关的G蛋白偶联受体的效应器发挥作用，激活RhoA。在缺乏Lsc的情况下，白细胞迁移受损，B淋巴细胞不能有效地解决整合素介导的黏附问题。在这里，我们证明Lsc在原代B淋巴细胞中以类似于同型四聚体的大分子量复合物形式生理性存在。干扰这种大分子量Lsc寡聚体的组装会导致Lsc两种功能活性的激活，并导致细胞变圆和整合素介导的黏附受到抑制。在细胞在整合素配体上迁移的过程中，我们发现Lsc主要定位于迁移细胞的后部，我们认为它在那里激活RhoA以解决整合素介导的黏附问题。这些数据共同表明，Lsc在迁移细胞的后缘调节整合素介导的黏附事件。
