The laminin-nidogen complex is a ligand for a specific splice isoform of the transmembrane protein tyrosine phosphatase LAR.
Leukocyte antigen-related protein (LAR) is a prototype for a family of transmembrane protein tyrosine phosphatases whose extracellular domain is composed of three Ig and several fibronectin type III (FnIII) domains. Complex alternative splicing of the LAR-FnIII domains 4-8 has been observed. The extracellular matrix laminin-nidogen complex was identified as a ... ligand for the LAR-FnIII domain 5 (Fn5) using a series of GST-LAR-FnIII domain fusion proteins and testing them in in vitro ligand-binding assays. LAR- laminin-nidogen binding was regulated by alternative splicing of a small exon within the LAR-Fn5 so that inclusion of this exon sequence resulted in disruption of the laminin-nidogen-binding activity. Long cellular processes were observed when HeLa cells were plated on laminin-nidogen, but not when plated on a fibronectin surface. Indirect immunofluorescent antibody staining revealed high expression of LAR in a punctate pattern, throughout the length of these cellular processes observed on laminin-nidogen. Antibody-induced cross-linking of LAR inhibited formation of these cellular processes, and inhibition was correlated with changes in cellular actin cytoskeletal structure. Thus, LAR-laminin-nidogen binding may play a role in regulating cell signaling induced by laminin-nidogen, resulting in cell morphological changes.
Mesh Terms:
Alternative Splicing, Binding Sites, Fibronectins, Hela Cells, Humans, Isoenzymes, Laminin, Ligands, Membrane Glycoproteins, Membrane Proteins, Protein Tyrosine Phosphatases, Receptor-Like Protein Tyrosine Phosphatases, Class 4, Receptors, Cell Surface, Recombinant Fusion Proteins, Tumor Cells, Cultured
Alternative Splicing, Binding Sites, Fibronectins, Hela Cells, Humans, Isoenzymes, Laminin, Ligands, Membrane Glycoproteins, Membrane Proteins, Protein Tyrosine Phosphatases, Receptor-Like Protein Tyrosine Phosphatases, Class 4, Receptors, Cell Surface, Recombinant Fusion Proteins, Tumor Cells, Cultured
J. Cell Biol.
Date: Jun. 29, 1998
PubMed ID: 9647658
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