鑑定CXCL14趨化因子可能的接受器

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Title:	鑑定CXCL14趨化因子可能的接受器 Identification for putative receptors of CXCL14
Authors:	康蕓涵
Contributors:	免疫學研究所碩士班
Keywords:	趨化因子 CXCL14
Date:	2011-07-14
Issue Date:	2011-10-17 16:36:09 (UTC+8)
Publisher:	中國醫藥大學
Abstract:	趨化因子是由細胞所分泌的小型細胞激素，他們能夠直接誘導附近的細胞進行趨化反應。趨化因子家族他們具有共同的特徵結構：約8-10道爾頓的大小，具有四個胱胺酸保留區。趨化因子藉由與G蛋白質連接的穿模蛋白質接受器，稱為趨化因子接受器來進行其生物學上的影響。趨化因子家族的其中一個成員是CXC趨化因子。他們的第一和第二個個保留的胱胺酸中間會有一個任意的胺基酸將兩個胱胺酸分開，這個胺基酸我們將其稱為X做為代表。目前，已經有17個 CXC趨化因子成員由哺乳動物中被鑑定出來，部份成員專一的接受器也已被確認，將其分別命名為CXCR1至CXCR7。CXC趨化因子14 (CXCL14) 是一個屬於CXC趨化因子家族的小型細胞激素，另有別名為BRAK (表示在胸部及腎臟都會表現的趨化因子)。CXCL14保有許多CXC趨化因子家族亞型的特色，但也有少部分的差異，例如有短的N端和在第三和第四個胱胺酸之間多了五個胺基酸的序列。CXCL14通常在正常的組織中會大量表現，而細胞的來源大多是由纖維母細胞所分泌。然而在腫瘤組織中CXCL14是少量表現或不存在於腫瘤組織中。這個趨化因子能夠在發炎反應中的調控子-前列腺素E2 (PGE-2)存在下，趨化單核球細胞及活化此類細胞。此外CXCL14也是樹突細胞的趨化及活化因子，並能使這些細胞歸巢，而CXCL14也能刺激活化的自然殺手細胞的遷移。CXCL14能夠抑制血管的新生，這個結果可能是因為阻止了內皮細胞的趨化作用。CXCL14基因存在於人類第五號色體上，具有4個外顯子。CXCL14在免疫系統的活化和對抗腫瘤上扮演一個重要的角色。然而，CXCL14的接受器尚未被鑑定出來。為了能更了解CXCL14的功能和其訊息傳遞路徑，於是我們想研究CXCL14可能的接受器。我們藉由共同免疫沉澱法和接受器結合力分析試驗確定了已知CXCL12的接受器CXCR4，也是CXCL14可能的接受器之一。 Chemokines are small cytokines secreted by cells. They have ability to induce directed chemotaxis in nearby responsive cells. Chemokine families share structural characteristics such as 8-10 kilodaltons in size, and the presence of four cysteine residues in conserved locations. Chemokine exert their biological effects by interacting with G protein-linked transmembrane receptors called chemokine receptors. One of the members of chemokine families is CXC chemokines. Their first two cysteine residues are separated by one amino acid, represented in this name with an "X". Presently, there are 17 different CXC chemokines described in mammals. They bind to CXC chemokine receptors, of which seven have been identified to date, named CXCR1 to CXCR7. Chemokine ligand 14 (CXCL14) is a small cytokine belonging to the CXC chemokine family that is also known as BRAK (for breast and kidney-expressed chemokine). Mature CXCL14 has many of the conserved features of the CXC chemokine subfamily but has some differences too, such as a shorter N-terminus and five extra amino acids in the region between its third and fourth cysteines. CXCL14 is constitutively expressed at high levels in many normal tissues, where its cellular source is thought to be fibroblasts. However, it is reduced or absent from most cancer cells. This chemokine is chemotactic for monocytes and can activate these cells in the presence of an inflammatory mediator called prostaglandin-E2 (PGE2). It is also a potent chemoattractant and activator of dendritic cells, is implicated in homing of these cells, and can stimulate the migration of activated NK cells. CXCL14 also inhibits angiogenesis, possibly as a result of its ability to block endothelial cell chemotaxis. The gene for CXCL14 contains four exons and is located on chromosome 5 in humans. CXCL14 plays important roles in anti-cancer and immune system activation. However, the receptor of CXCL14 has not yet been identified. To bettrer understand the function and signal transduction pathway of CXCL14, the potential receptors for CXCL14 were studies. We confirmed that the known receptors for CXCL12, CXCR4, are also putative receptors for CXCL14 by using co-immunoprecipitation assays and receptor binding assay.
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