Perez Omar D, Kinoshita Shigemi, Hitoshi Yasumichi, Payan Donald G, Kitamura Toshio, Nolan Garry P, Lorens James B
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Immunity. 2002 Jan;16(1):51-65. doi: 10.1016/s1074-7613(02)00266-2.
We identified intracellular adhesion molecule-2 (ICAM-2) in a genetic screen as an activator of the PI3K/AKT pathway leading to inhibition of apoptosis. ICAM-2 induced tyrosine phosphorylation of ezrin and PI3K kinase membrane translocation, resulting in phosphatidylinositol 3,4,5 production, PDK-1 and AKT activation, and subsequent phosphorylation of AKT targets BAD, GSK3, and FKHR. ICAM-2 clustering protected primary human CD19+ cells from TNFalpha- and Fas-mediated apoptosis as determined by single-cell analysis. ICAM-2 engagement by CD19+ cells of its natural receptor, LFA-1, on CD4+ naive cells specifically induced AKT activity in the absence of an MHC-peptide interaction. These results attribute a novel signaling function to ICAM-2 that might suggest mechanisms by which ICAM-2 signals intracellular communication at various immunological synapses.
我们在一项基因筛选中鉴定出细胞间黏附分子2（ICAM-2）是导致细胞凋亡抑制的PI3K/AKT信号通路的激活剂。ICAM-2诱导埃兹蛋白的酪氨酸磷酸化和PI3K激酶的膜转位，导致磷脂酰肌醇3,4,5的产生、PDK-1和AKT的激活，以及随后AKT靶标BAD、GSK3和FKHR的磷酸化。单细胞分析表明，ICAM-2聚集可保护原代人CD19+细胞免受TNFα和Fas介导的细胞凋亡。CD19+细胞与其天然受体LFA-1在CD4+幼稚细胞上的结合，在没有MHC-肽相互作用的情况下特异性诱导AKT活性。这些结果赋予ICAM-2一种新的信号功能，这可能提示ICAM-2在各种免疫突触处进行细胞内通讯的信号传导机制。
