Yamashita Y, Fukuta D, Tsuji A, Nagabukuro A, Matsuda Y, Nishikawa Y, Ohyama Y, Ohmori H, Ono M, Takai T
Department of Biotechnology, Faculty of Engineering Okayama University, Tsushima-Naka.
J Biochem. 1998 Feb;123(2):358-68. doi: 10.1093/oxfordjournals.jbchem.a021945.
Recently, we found a novel murine cell-surface glycoprotein, designated as p91, expressed mainly in myeloid cells such as macrophages and mast cells. The molecule has six immunoglobulin-like extracellular domains, a transmembrane segment, and a cytoplasmic tail containing four immunoreceptor tyrosine-based inhibition motif (ITIM) or ITIM-like sequences, resembling the structural features of human killer-cell inhibitory receptors (KIR). Here we show that p91 comprises a polymorphic gene family, harboring one potent inhibitory-type p91 and at least two other p91 genes. Tyrosine-phosphorylated, but not nonphosphorylated, synthetic peptides matching the third ITIM and the fourth ITIM-like sequences, respectively, found in the cytoplasmic portion of p91A, the sole inhibitory-type p91, were associated with the tyrosine phosphatases, SHP-1 and SHP-2. In addition, the phosphotyrosyl peptide matching the third ITIM sequence also bound the inositol 5-phosphatase, SHIP. These results support the notion that p91A may function as an inhibitory cell-surface molecule against cell activation. The p91 genes were shown to be clustered in the proximal region of mouse chromosome 7, a syntenic position of human chromosome 19 where the genes for the KIR family are found. A human cDNA clone cross-hybridizing to a murine p91 probe was isolated from a human spleen cDNA library, and was found to code for a molecule quite similar to members of the immunoglobulin-like transcript (or ILT) family. The gene was found to be located on human chromosome 19q13.3-13.4. These results establish the existence of a novel set of potent regulatory receptors in mouse and man, similar but different from the KIR family.
最近，我们发现了一种新的小鼠细胞表面糖蛋白，命名为p91，主要在巨噬细胞和肥大细胞等髓系细胞中表达。该分子具有六个免疫球蛋白样细胞外结构域、一个跨膜区段和一个含有四个基于免疫受体酪氨酸的抑制基序（ITIM）或ITIM样序列的胞质尾部，类似于人类杀伤细胞抑制受体（KIR）的结构特征。在此我们表明，p91包含一个多态基因家族，有一个强效抑制型p91和至少两个其他p91基因。分别与p91A（唯一的抑制型p91）胞质部分中发现的第三个ITIM和第四个ITIM样序列匹配的酪氨酸磷酸化而非非磷酸化的合成肽，与酪氨酸磷酸酶SHP-1和SHP-2相关。此外，与第三个ITIM序列匹配的磷酸酪氨酸肽也结合肌醇5-磷酸酶SHIP。这些结果支持p91A可能作为一种抑制细胞表面分子对抗细胞活化的观点。p91基因被证明聚集在小鼠7号染色体的近端区域，这是人类19号染色体上发现KIR家族基因的同线位置。从人脾脏cDNA文库中分离出一个与小鼠p91探针交叉杂交的人cDNA克隆，发现它编码一个与免疫球蛋白样转录本（或ILT）家族成员非常相似的分子。该基因位于人类19号染色体的19q13.3-13.4。这些结果证实了在小鼠和人类中存在一组新的强效调节受体，它们与KIR家族相似但不同。
