A new role for platelet-endothelial cell adhesion molecule-1 (CD31): inhibition of TCR-mediated signal transduction.
A new role for platelet-endothelial cell adhesion molecule-1 (CD31): inhibition of TCR-mediated signal transduction.
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DOI：
10.4049/jimmunol.163.2.682
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发表时间：
1999-07
影响因子：
4.4
通讯作者：
D. Newton-Nash;P. Newman
中科院分区：
文献类型：
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作者：
D. Newton-Nash;P. Newman
血小板-内皮细胞粘附分子-1（PECAM-1）是由内皮细胞、血小板、单核细胞、中性粒细胞和某些T细胞亚群表达的130 kDa跨膜糖蛋白。PECAM-1胞外结构域具有六个Ig同源结构域，其与细胞粘附分子共享序列相似性。PECAM-1胞质结构域含有基于免疫受体酪氨酸的抑制基序（ITIM），当适当接合时，其在酪氨酸残基上磷酸化，为非跨膜、Src同源2结构域的蛋白酪氨酸磷酸酶（SHP）-1和SHP-2创建对接位点。本研究的目的是确定PECAM-1是否抑制蛋白酪氨酸激酶（PTK）依赖的信号转导介导的免疫受体酪氨酸为基础的活化基序含有TCR。将共表达PECAM-1和TCR/CD 3复合物的Jurkat细胞进行INDO-1AM标记，然后与抗CD 3 β mAb、抗PECAM-1 mAb或两者一起孵育，并使用山羊抗小鼠IgG交联表面结合的mAb。发现由CD 3交联诱导的钙动员通过PECAM-1的共连接以剂量依赖性方式减弱。PECAM-1介导的TCR信号传导抑制至少部分归因于抑制钙从细胞内储存释放。这些数据提供了PECAM-1可以抑制由含ITAM的受体转导的信号的证据，并支持将PECAM-1纳入含ITIM的PTK依赖性信号转导抑制剂家族。
Platelet-endothelial cell adhesion molecule-1 (PECAM-1) is a 130-kDa transmembrane glycoprotein expressed by endothelial cells, platelets, monocytes, neutrophils, and certain T cell subsets. The PECAM-1 extracellular domain has six Ig-homology domains that share sequence similarity with cellular adhesion molecules. The PECAM-1 cytoplasmic domain contains an immunoreceptor tyrosine-based inhibitory motif (ITIM) that, when appropriately engaged, becomes phosphorylated on tyrosine residues, creating docking sites for nontransmembrane, Src homology 2 domain-bearing protein tyrosine phosphatase (SHP)-1 and SHP-2. The purpose of the present study was to determine whether PECAM-1 inhibits protein tyrosine kinase (PTK)-dependent signal transduction mediated by the immunoreceptor tyrosine-based activation motif-containing TCR. Jurkat cells, which coexpress PECAM-1 and the TCR/CD3 complex, were INDO-1AM-labeled and then incubated with anti-CD3epsilon mAbs, anti-PECAM-1 mAbs, or both, and goat anti-mouse IgG was used to cross-link surface-bound mAbs. Calcium mobilization induced by CD3 cross-linking was found to be attenuated by coligation of PECAM-1 in a dose-dependent manner. PECAM-1-mediated inhibition of TCR signaling was attributable, at least in part, to inhibition of release of calcium from intracellular stores. These data provide evidence that PECAM-1 can dampen signals transduced by ITAM-containing receptors and support inclusion of PECAM-1 within the family of ITIM-containing inhibitors of PTK-dependent signal transduction.