Lee D M, Patel D D, Pendergast A M, Haynes B F
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Int Immunol. 1996 Aug;8(8):1195-203. doi: 10.1093/intimm/8.8.1195.
Human CD7 is a 40 kDa protein expressed on thymocytes, early T, B, NK and myeloid lineage cells in bone marrow, and on mature T and NK cells. Previous studies suggested human CD7 may be involved in T and NK cell activation and/or adhesion, and that CD7-mediated cell activation may be transduced via the lipid kinase phosphatidylinositol 3-kinase (Pi3-kinase), a heterodimeric cytosolic protein consisting of an 85 kDa adaptor subunit that is coupled to a 110 kDa catalytic subunit. It has recently been shown that a sequence motif present in the cytoplasmic tall of both human and mouse CD7 bound with high affinity to recombinant SH2 domains present in the p85 subunit of Pi3-kinase. In this work, we used co-precipitation with anti-CD7 mAb 3A1 and recombinant p85 SH2-GST fusion proteins and peptide competition analysis to demonstrate that the cytoplasmic tail of CD7 interacts with a functional Pi3-kinase via the pTyr-X-X-Met motif. Furthermore, we show that cross-linking of CD7 markedly increased the amount of Pi3-kinase activity associated with CD7. The interaction of CD7 with the Pi3-kinase signal transduction pathway provides a mechanism for the previously observed functional responses attributed to CD7-mediated T and NK cell activation.
人CD7是一种40 kDa的蛋白质，表达于胸腺细胞、早期T细胞、B细胞、骨髓中的NK细胞和髓系细胞以及成熟T细胞和NK细胞上。先前的研究表明，人CD7可能参与T细胞和NK细胞的激活和/或黏附，并且CD7介导的细胞激活可能通过脂质激酶磷脂酰肌醇3激酶（Pi3激酶）进行转导，Pi3激酶是一种异二聚体细胞溶质蛋白，由一个与110 kDa催化亚基偶联的85 kDa接头亚基组成。最近有研究表明，人和小鼠CD7胞质尾部存在的一个序列基序与Pi3激酶p85亚基中存在的重组SH2结构域具有高亲和力结合。在这项研究中，我们使用抗CD7单克隆抗体3A1和重组p85 SH2-GST融合蛋白进行共沉淀以及肽竞争分析，以证明CD7的胞质尾部通过pTyr-X-X-Met基序与功能性Pi3激酶相互作用。此外，我们还表明，CD7的交联显著增加了与CD7相关的Pi3激酶活性的量。CD7与Pi3激酶信号转导途径的相互作用为先前观察到的归因于CD7介导的T细胞和NK细胞激活的功能反应提供了一种机制。
