title: Cloning, expression, characterization, and role in autocrine cell growth of cell surface retention sequence binding protein-1.
abstract: 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 approximately 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.
authors.affiliation: Departments of Biochemistry and Molecular Biology, St. Louis University School of Medicine, St. Louis, Missouri 63104, USA. huangjs@slu.edu
authors.forename: Shuan Shian
authors.initials: SS
authors.lastname: Huang
authors.forename: Fen-Mei
authors.initials: FM
authors.lastname: Tang
authors.forename: Yen-Hua
authors.initials: YH
authors.lastname: Huang
authors.forename: I-Hua
authors.initials: IH
authors.lastname: Liu
authors.forename: Shih-Chi
authors.initials: SC
authors.lastname: Hsu
authors.forename: Shui-Tein
authors.initials: ST
authors.lastname: Chen
authors.forename: Jung San
authors.initials: JS
authors.lastname: Huang
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002417:Cattle; D002455:Cell Division; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D003902:Detergents / Q000494:pharmacology; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry; D005347:Fibroblasts / Q000378:metabolism; D015723:Gene Library; D006023:Glycoproteins / Q000737:chemistry; D006801:Humans; D015151:Immunoblotting; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D017830:Octoxynol / Q000494:pharmacology; D020575:Oncogene Proteins v-sis / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D021382:Protein Sorting Signals; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014162:Transfection
chemical_list: D018076:DNA, Complementary; D003902:Detergents; D004220:Disulfides; D006023:Glycoproteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D008565:Membrane Proteins; D020575:Oncogene Proteins v-sis; D010455:Peptides; D021382:Protein Sorting Signals; C091632:cell-surface retention-binding protein 1; D017830:Octoxynol