title: Syndecan-2 is a novel ligand for the protein tyrosine phosphatase receptor CD148.
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.
authors.affiliation: Centre for Microvascular Research, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, United Kingdom. j.whiteford@qmul.ac.uk
authors.forename: James R
authors.initials: JR
authors.lastname: Whiteford
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Xian
authors.forename: Claire
authors.initials: C
authors.lastname: Chaussade
authors.forename: Bart
authors.initials: B
authors.lastname: Vanhaesebroeck
authors.forename: Sussan
authors.initials: S
authors.lastname: Nourshargh
authors.forename: John R
authors.initials: JR
authors.lastname: Couchman
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D019169:Jurkat Cells; D008024:Ligands; D008168:Lung / Q000166:cytology; D051379:Mice; D018919:Neovascularization, Physiologic / Q000235:genetics; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D034741:RNA, Small Interfering; D051381:Rats; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D053669:Syndecan-2 / Q000235:genetics / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D019012:Integrin beta1; D008024:Ligands; D034741:RNA, Small Interfering; D053669:Syndecan-2; D058539:Phosphatidylinositol 3-Kinase; D019061:src-Family Kinases; C486288:PTPRJ protein, human; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3