EXPRESSION OF THE GP49 FAMILY ON MAST CELLS AND MONONUCLEAR PHAGOCYTES

gp 49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 和单核吞噬细胞。两个高度同源的基因gp 49 A和gp 49 B， 编码gp 49家族的至少三个转录成员。的 gp 49 A基因编码gp 49 A1转录物，而gp 49 B基因编码 gp 49 B1和gp 49 B2交替转录物。gp 49 B1蛋白表达于 肥大细胞的表面，而gp 49 B2蛋白可能被分泌。后 用佛波醇肉豆蔻酸酯乙酸酯或IgE激活肥大细胞， 丝氨酸磷酸化，与蛋白激酶的存在一致 C磷酸化位点在胞质结构域的一个丝氨酸上。这 gp 49 B1的结构域，而不是gp 49 A1的结构域，也含有潜在的 磷酸化酪氨酸，是共有序列的重要部分 IG的某些受体进行信号转导所必需的 超家族gp 49家族的一个潜在的人类成员已经被确定。 同源cDNA克隆。gp 49 A1或gp 49 B1蛋白的过表达 在表达低天然水平gp 49的肥大细胞中的转染 蛋白质导致它们的聚集显著增加， 辅助性T细胞（Th）。因此，gp 49蛋白质家族可能 代表由肥大细胞表达的一类新的粘附分子， 单核吞噬细胞，可能有助于其与Th的相互作用， 也许是其他细胞。拟议研究的总体目标是 了解更多关于gp 49蛋白质家族成员如何介导 细胞聚集/粘附，以便了解它们的 可能参与细胞间的相互作用， 肥大细胞/单核吞噬细胞和表达 反配体。因此，提出研究的具体目标 1）确定gp 49 A1和gp 49 B1蛋白参与 细胞-细胞粘附，并鉴定表达反配体的细胞， gp 49蛋白质家族; 2）定义 重组可溶性gp 49 B2蛋白与表达抗衡配体的细胞， 并评估gp 49 B2蛋白从哺乳动物细胞的分泌; 3） 为成员定义特定转录物和蛋白质的表达 在肥大细胞和单核吞噬细胞中， 4）确定小鼠gp 49与小鼠gp 49之间的关系。 家族和gp 49 B1-样人cDNA的表达， 反配体表达和可能的功能。预计各国 拟议研究的成功完成将加速 认识和理解的功能范围介导的 IG超家族的gp 49亚家族。因为肥大细胞和T细胞 在支气管哮喘的发病机制中起作用， 建立，拟议的研究涉及的总主题， 通过建立新的互动机制， 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.