Syndecan-2 is a novel ligand for the protein tyrosine phosphatase receptor CD148

TY - JOUR

T1 - Syndecan-2 is a novel ligand for the protein tyrosine phosphatase receptor CD148

AU - Whiteford, James R

AU - Xian, Xiaojie

AU - Chaussade, Claire

AU - Vanhaesebroeck, Bart

AU - Nourshargh, Sussan

AU - Couchman, John R

PY - 2011/10/1

Y1 - 2011/10/1

N2 - 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.

AB - 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.

KW - Animals

KW - Antigens, CD29

KW - Cell Adhesion

KW - Cell Line

KW - Cytoskeleton

KW - Fibroblasts

KW - Gene Expression Regulation

KW - Humans

KW - Inflammation

KW - Jurkat Cells

KW - Ligands

KW - Lung

KW - Mice

KW - Neovascularization, Physiologic

KW - Phosphatidylinositol 3-Kinase

KW - Protein Interaction Domains and Motifs

KW - RNA, Small Interfering

KW - Rats

KW - Receptor-Like Protein Tyrosine Phosphatases, Class 3

KW - Signal Transduction

KW - Syndecan-2

KW - src-Family Kinases

U2 - 10.1091/mbc.E11-02-0099

DO - 10.1091/mbc.E11-02-0099

M3 - Journal article

C2 - 21813734

SN - 1059-1524

VL - 22

SP - 3609

EP - 3624

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

IS - 19

ER -