Bandari Persis S, Qian Jing, Yehia Ghassan, Joshi Deval D, Maloof Paul B, Potian Julius, Oh Hyun S, Gascon Pedro, Harrison Jonathan S, Rameshwar Pranela
Department of Obstetrics, Gynecology and Women's Health, UMDNJ-New Jersey Medical School, Newark, NJ, USA.
Regul Pept. 2003 Mar 28;111(1-3):169-78. doi: 10.1016/s0167-0115(02)00288-4.
Neurokinin 1 (NK-1) is a member of seven transmembrane G protein-coupled receptors. NK-1 interacts with peptides belonging to the tachykinin family and showed preference for substance P (SP). NK-1 is induced in bone marrow (BM) stroma. NK-1-SP interactions could lead to changes in the functions of lymphohematopoietic stem cell (LHSC). This report describes the cloning and characterization of a cDNA clone isolated after screening of three cDNA libraries with an NK-1-specific probe. Based on its expression, the cDNA clone was designated hematopoietic growth factor inducible neurokinin-1 type (HGFIN). Computational analyses predicted that HGFIN is transmembrane with the carboxyl terminal extracellular. Proteomic studies with purified HGFIN and SP showed noncovalent interactions. HGFIN-SP interactions were supported by transient expression of HGFIN in CHO cells. Transient expression of HGFIN in unstimulated BM fibroblasts led to the induction of endogenous NK-1. Since NK-1 expression in BM fibroblasts requires cell stimulation, these studies suggest that there might be intracellular crosstalk between NK-1 and HGFIN. Northern analyses with total RNA from different BM cell subsets showed that HGFIN was preferentially expressed in differentiated cells. This suggests that HGFIN might be involved in the maturation of LHSC. HGFIN was detected in several other tissues, but not in brain where NK-1 is constitutively expressed.
神经激肽1（NK-1）是七跨膜G蛋白偶联受体家族的一员。NK-1与速激肽家族的肽相互作用，并对P物质（SP）表现出偏好。NK-1在骨髓（BM）基质中被诱导表达。NK-1与SP的相互作用可能导致淋巴细胞造血干细胞（LHSC）功能的改变。本报告描述了用NK-1特异性探针筛选三个cDNA文库后分离得到的一个cDNA克隆的克隆及特性鉴定。根据其表达情况，该cDNA克隆被命名为造血生长因子诱导神经激肽-1型（HGFIN）。计算分析预测HGFIN是跨膜蛋白，其羧基末端位于细胞外。对纯化的HGFIN和SP进行的蛋白质组学研究显示它们之间存在非共价相互作用。HGFIN在CHO细胞中的瞬时表达证实了HGFIN与SP的相互作用。在未受刺激的BM成纤维细胞中瞬时表达HGFIN可诱导内源性NK-1的表达。由于BM成纤维细胞中NK-1的表达需要细胞刺激，这些研究表明NK-1和HGFIN之间可能存在细胞内串扰。对来自不同BM细胞亚群的总RNA进行的Northern分析表明，HGFIN在分化细胞中优先表达。这表明HGFIN可能参与LHSC的成熟过程。在其他几种组织中检测到了HGFIN，但在组成性表达NK-1的脑中未检测到。
