Cloning, expression, characterization, and role in autocrine cell growth of cell surface retention sequence binding protein-1
Cloning, expression, characterization, and role in autocrine cell growth of cell surface retention sequence binding protein-1
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DOI：
10.1074/jbc.m306411200
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发表时间：
2003-10-31
影响因子：
4.8
通讯作者：
Huang, JS
中科院分区：
文献类型：
--
作者：
Huang, SS;Tang, FM;Huang, JS
细胞表面保留序列结合蛋白-1 （CRSBP-1）是v-sis基因产物（血小板衍生生长因子- bb）的细胞表面保留序列（CRS）基序的细胞表面结合蛋白。它已被证明在v-sis转化细胞（成纤维细胞）中负责v-sis基因产物的细胞表面保留，并被假设在这些细胞的自分泌生长和转化中发挥作用。从牛肝脏文库中克隆的CRSBP-1 cDNA编码322个残基的I型膜蛋白，其中包含23个残基的信号肽、215个残基的细胞表面结构域、21个残基的跨膜结构域和63个残基的细胞质结构域。在转染细胞中表达的CRSBP-1是一种类似于120 kda二硫化物连接的二聚体糖蛋白，并表现出双配体（含crs的生长调节剂（v-sis基因产物和胰岛素样生长因子结合蛋白-3，IGFBP-3）和透明质酸）的结合活性。CRSBP-1过表达（通过稳定转染CRSBP-1 cDNA的细胞）增强v-sis转化细胞的自分泌环信号、细胞生长和致瘤性（在小鼠中）。在人肺癌细胞（H1299细胞）中，CRSBP-1的表达也增强了IGFBP-3介导的自分泌细胞生长，而H1299细胞表达很少（如果有的话）内源性CRSBP-1，并对外源性IGFBP-3表现出有丝分裂反应，稳定转染IGFBP-3 cDNA。然而，CRSBP-1过表达并不影响不产生这些含crs生长调节剂的正常细胞和转化细胞的生长。这些结果表明，CRSBP-1在含有CRS的生长调节剂介导的细胞生长的自分泌调节中发挥作用。
Cell surface retention sequence binding protein-1 (CRSBP-1) is a cell surface binding protein for the cell surface retention sequence (CRS) motif of the v-sis gene product (platelet-derived growth factor-BB). It has been shown to be responsible for cell surface retention of the v-sis gene product in v-sis-transformed cells ( fibroblasts) and has been hypothesized to play a role in autocrine growth and transformation of these cells. Here we demonstrate that the CRSBP-1 cDNA cloned from bovine liver libraries encodes a 322-residue type I membrane protein containing a 23-residue signal peptide, a 215-residue cell surface domain, a 21-residue transmembrane domain, and a 63-residue cytoplasmic domain. CRSBP-1 expressed in transfected cells is an similar to 120-kDa disulfide-linked homodimeric glycoprotein and exhibits dual ligand (CRS-containing growth regulators (v-sis gene product and insulin-like growth factor binding protein-3, IGFBP-3) and hyaluronic acid) binding activity. CRSBP-1 overexpression (by stable transfection of cells with CRSBP-1 cDNA) enhances autocrine loop signaling, cell growth, and tumorigenicity ( in mice) of v-sis-transformed cells. CRSBP-1 expression also enhances autocrine cell growth mediated by IGFBP-3 in human lung carcinoma cells (H1299 cells), which express very little, if any, endogenous CRSBP-1 and exhibits a mitogenic response to exogenous IGFBP-3, stably transfected with IGFBP-3 cDNA. However, CRSBP-1 overexpression does not affect growth of normal and transformed cells that do not produce these CRS-containing growth regulators. These results suggest that CRSBP-1 plays a role in autocrine regulation of cell growth mediated by growth regulators containing CRS.