Division of Biochemistry and Biotechnology, Department of Biosciences, University of Helsinki, 00014 Helsinki, Finland.
J Immunol. 2011 Oct 1;187(7):3613-9. doi: 10.4049/jimmunol.1100704. Epub 2011 Aug 29.
Adhesion is pivotal for most leukocyte functions, and the β(2) integrin family of adhesion molecules plays a central role. The integrins need activation to become functional, but the molecular events resulting in adhesion have remained incompletely understood. In human T cells, activation through the TCR results in specific phosphorylation of the T758 on the β(2) chain of LFA-1. We now show that this phosphorylation leads to downstream binding of 14-3-3 proteins, followed by engagement of the guanine nucleotide exchange factor protein Tiam1 and Rac1 activation. Downregulation of the signaling molecules inhibits LFA-1 activity. Activation by the chemokine stromal cell-derived factor-1α also results in T758 phosphorylation and integrin activation. Thus, TCR and chemokine activation converges on LFA-1 phosphorylation, followed by similar downstream events affecting adhesion.
黏附对于大多数白细胞功能至关重要，而β(2)整合素家族的黏附分子则起着核心作用。整合素需要激活才能发挥功能，但导致黏附的分子事件仍不完全清楚。在人类 T 细胞中，通过 TCR 的激活导致 LFA-1 的β(2)链上 T758 的特异性磷酸化。我们现在表明，这种磷酸化导致随后与 14-3-3 蛋白结合，然后与鸟嘌呤核苷酸交换因子蛋白 Tiam1 结合并激活 Rac1。信号分子的下调抑制了 LFA-1 的活性。趋化因子基质细胞衍生因子-1α的激活也导致 T758 磷酸化和整合素激活。因此，TCR 和趋化因子的激活都集中在 LFA-1 的磷酸化上，随后发生类似的下游事件影响黏附。
