Faculty Collaboration Database

Lysosomal integral membrane protein II binds thrombospondin-1. Structure-function homology with the cell adhesion molecule CD36 defines a conserved recognition motif. J Biol Chem 1998 Feb 27;273(9):4855-63

Date

03/28/1998

Pubmed ID

9478926

DOI

10.1074/jbc.273.9.4855

Scopus ID

2-s2.0-0032570699 (requires institutional sign-in at Scopus site)   55 Citations

Abstract

LIMPII (lysosomal integral membrane protein II) is one of a family of proteins structurally related to the cell surface glycoprotein CD36. We recently defined a single structural domain on CD36 that mediates binding to adhesive glycoprotein thrombospondin-1 (TSP1). The CD36-TSP1 interaction is known to play a role in platelet-tumor and platelet-monocyte adhesion, angiogenesis, and in monocyte uptake of apoptotic cells. To test whether LIMPII also binds TSP1, a LIMPII peptide corresponding to the TSP1 binding domain of CD36 was expressed as a recombinant glutathione S-transferase (GST) fusion protein. In solid phase binding assays, purified 125I-TSP1 bound to immobilized GST/LIMPII in a time-dependent and saturable manner. Inhibition by excess unlabeled TSP1 or EDTA demonstrated specificity. LIMPII.TSP1 complex formation was specifically blocked by soluble LIMPII fusion protein, by monospecific rabbit IgG directed against the LIMPII peptide and by CD36 fusion proteins containing the TSP1 binding domain. Transfection of Bowes melanoma cells with a chimeric LIMPII cDNA that targets expression to the plasma membrane conferred the ability to bind 125I-TSP1 and to adhere to TSP1-coated surfaces. This study defines a TSP1 binding site conserved between LIMPII and CD36 and suggests that cell surface LIMPII may function in some circumstances as an adhesion receptor for TSP1. Computer-assisted homology searches suggest that the TSP1 recognition motif identified from study of CD36 family members may be widely expressed in nature.

Author List

Crombie R, Silverstein R

Author

Roy L. Silverstein MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Animals
Binding Sites
Binding, Competitive
Blood Platelets
CD36 Antigens
Cell Compartmentation
Conserved Sequence
Evolution, Molecular
Lysosomes
Melanoma, Experimental
Membrane Glycoproteins
Molecular Sequence Data
Protein Binding
Rats
Rats, Sprague-Dawley
Recombinant Fusion Proteins
Sequence Homology, Amino Acid
Thrombospondin 1
Transfection
Tumor Cells, Cultured