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: Shuan Shian Huang, Fen-Mei Tang, Yen-Hua Huang, I-Hua Liu, Shih-Chi Hsu, Shui-Tein Chen, Jung San Huang
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 278 Issue 44 Pg. 43855-69 (Oct 31 2003) ISSN: 0021-9258 [Print] United States
• PMID: 12912978 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA, Complementary
• Detergents
• Disulfides
• Glycoproteins
• Insulin-Like Growth Factor Binding Protein 3
• Membrane Proteins
• Oncogene Proteins v-sis
• Peptides
• Protein Sorting Signals
• cell-surface retention-binding protein 1
• Octoxynol

Topics

• Amino Acid Motifs
• Amino Acid Sequence
• Animals
• Base Sequence
• Blotting, Western
• Cattle
• Cell Division
• Cell Line, Transformed
• Cell Line, Tumor
• Cytoplasm (metabolism)
• DNA, Complementary (metabolism)
• Detergents (pharmacology)
• Dimerization
• Disulfides (chemistry)
• Fibroblasts (metabolism)
• Gene Library
• Glycoproteins (chemistry)
• Humans
• Immunoblotting
• Insulin-Like Growth Factor Binding Protein 3 (metabolism)
• Liver (metabolism)
• Membrane Proteins (biosynthesis, genetics, physiology)
• Mice
• Molecular Sequence Data
• NIH 3T3 Cells
• Octoxynol (pharmacology)
• Oncogene Proteins v-sis (metabolism)
• Peptides (chemistry)
• Protein Binding
• Protein Sorting Signals
• Sequence Homology, Amino Acid
• Time Factors
• Transfection