EXPRESSION OF THE GP49 FAMILY ON MAST CELLS AND MONONUCLEAR PHAGOCYTES

Gp49蛋白家族是免疫球蛋白(Ig)的成员。 在小鼠中由肥大细胞优先表达的超家族 和单核巨噬细胞。两个高度同源的基因gp49A和gp49B， 编码至少三个gp49家族转录成员。这个 Gp49A基因编码gp49A1转录本，而gp49B基因编码 Gp49B1和gp49B2交替转录本。Gp49B1蛋白在细胞上表达 肥大细胞表面可分泌gp49B2蛋白。vt.在.的基础上 用佛波酯或IgE激活肥大细胞，gp49B1是 丝氨酸被磷酸化，与蛋白激酶的存在一致 C磷酸化位点位于细胞质结构域的一个丝氨酸上。这 Gp49B1的结构域，而不是gp49A1的结构域，也包含一个潜在的 磷酸化酪氨酸是共识序列的重要组成部分 某些免疫球蛋白受体所需的信号转导 超级大家庭。已经确定了gp49家族的一个潜在人类成员。 通过同源基因的克隆。Gp49A1或gp49B1蛋白的过表达 在低水平表达gp49的肥大细胞中的转染 蛋白质导致它们与蛋白质的聚集性显著增加 激活的辅助性T细胞(Th)。因此，gp49蛋白家族很可能 代表了一类由肥大细胞表达的新的黏附分子 单核巨噬细胞可能促进其与Th和Th的相互作用 也许是其他细胞。拟议研究的广泛目标是 了解更多关于gp49蛋白家族成员如何调节 细胞聚集/黏附，以获得对其 可能参与几个细胞之间的细胞间相互作用 肥大细胞/单核吞噬细胞和表达 反配体(S)。因此，拟议研究的具体目标是 L)研究gp49A1和gp49B1蛋白在细胞周期调控中的作用 细胞-细胞黏附，并鉴定表达反配体的细胞(S) 对于gp49蛋白家族；2)定义 用反配体表达细胞重组可溶性gp49B2蛋白， 检测哺乳动物细胞分泌gp49B2蛋白的能力；3) 确定成员的特定转录本和蛋白质的表达 小鼠肥大细胞和单核巨噬细胞中的gp49家族 以及4)确定小鼠gp49之间的关系。 家族和一个类似gp49B1的人cDNAs的细胞表达， 反配体的表达，以及可能的功能。预计 建议的研究将会加速完成。 认识和理解由 免疫球蛋白超家族中的gp49亚家族。因为肥大细胞和T细胞 在哮喘的发病机制中起着坚定的作用 已确定，拟议的研究与这一总体主题有关 通过建立一种新的机制来实现他们的互动和他们的 可能对炎症的协同作用，包括 航空公司。

The gp49 family of proteins are members of the immunoglobulin (Ig) superfamily that in the mouse are preferentially expressed by mast cells and mononuclear phagocytes. Two highly homologous genes, gp49A and gp49B, encode at least three transcriptional members of the gp49 family. The gp49A gene encodes gp49A1 transcripts, whereas the gp49B gene encodes gp49B1 and gp49B2 alternate transcripts. gp49B1 protein is expressed on the surface of mast cells, while gp49B2 protein may be secreted. Upon mast cell activation with phorbol myristate acetate or IgE, gp49B1 is serine phosphorylated, consistent with the presence of a protein kinase C phosphorylation site on one serine of the cytoplasmic domain. This domain of gp49B1, but not that of gp49A1, also contains a potentially phosphorylated tyrosine that is an essential part of a consensus sequence required for signal transduction by certain receptors of the Ig superfamily. A potential human member of the gp49 family has been defined by homology cDNA cloning. Over-expression of gp49A1 or gp49B1 protein by transfection in mast cells that express low native levels of gp49 proteins results in a substantial increase in their aggregation with activated T helper (Th) cells. Thus, the gp49 family of proteins likely represents a new class of adhesion molecules expressed by mast cells and mononuclear phagocytes that may facilitate their interaction with Th and perhaps other cells. The broad objective of the proposed research is to understand more about how members of the gp49 family of proteins mediate cell aggregation/adhesion, so as to gain an appreciation of their potential involvement in cell-cell interactions between several populations of mast cells/mononuclear phagocytes and cells that express a counterligand(s). Therefore, the specific aims of the proposed research are: l) to define the participation of gp49A1 and gp49B1 proteins in cell-cell adhesion, and to identify cells that express a counterligand(s) for the gp49 family of proteins; 2) to define the interactions of recombinant soluble gp49B2 protein with counterligand-expressing cells, and to assess the secretion of gp49B2 protein from mammalian cells; 3) to define the expression of specific transcripts and protein for members of the entire mouse gp49 family in mast cell and mononuclear phagocyte populations; and 4) to define the relationship between the mouse gp49 family and a gp49B1-like human cDNA in terms of cell expression, counterligand expression, and possible function. it is anticipated that the successful completion of the proposed studies will accelerate recognition and understanding of the range of functions mediated by the gp49 subfamily of the Ig superfamily. Because both mast cells and T cells have roles in the pathogenesis of bronchial asthma that are firmly established, the proposed studies relate to the overall theme of this program by establishing a new mechanism for their interaction and their possible synergistic contribution to inflammation, including that of the airways.