Abstract
Syndecan-2 is a heparan sulfate proteoglycan that has a cell adhesion regulatory domain contained within its extracellular core protein. Cell adhesion to the syndecan-2 extracellular domain (S2ED) is β1 integrin dependent; however, syndecan-2 is not an integrin ligand. Here the protein tyrosine phosphatase receptor CD148 is shown to be a key intermediary in cell adhesion to S2ED, with downstream β1 integrin-mediated adhesion and cytoskeletal organization. We show that S2ED is a novel ligand for CD148 and identify the region proximal to the transmembrane domain of syndecan-2 as the site of interaction with CD148. A mechanism for the transduction of the signal from CD148 to β1 integrins is elucidated requiring Src kinase and potential implication of the C2β isoform of phosphatidylinositol 3 kinase. Our data uncover a novel pathway for β1 integrin-mediated adhesion of importance in cellular processes such as angiogenesis and inflammation.
| Original language | English |
|---|---|
| Journal | Molecular Biology of the Cell |
| Volume | 22 |
| Issue number | 19 |
| Pages (from-to) | 3609-24 |
| Number of pages | 16 |
| ISSN | 1059-1524 |
| DOIs | |
| Publication status | Published - 1 Oct 2011 |
Keywords
- Animals
- Antigens, CD29
- Cell Adhesion
- Cell Line
- Cytoskeleton
- Fibroblasts
- Gene Expression Regulation
- Humans
- Inflammation
- Jurkat Cells
- Ligands
- Lung
- Mice
- Neovascularization, Physiologic
- Phosphatidylinositol 3-Kinase
- Protein Interaction Domains and Motifs
- RNA, Small Interfering
- Rats
- Receptor-Like Protein Tyrosine Phosphatases, Class 3
- Signal Transduction
- Syndecan-2
- src-Family Kinases