CD36 is a cell surface receptor that has been shown to interact with a large variety of ligands including thrombospondin, collagen, Plasmodium falciparum-infected erythrocytes, apoptotic neutrophils, modified low density lipoproteins, anionic phospholipids and long chain fatty acids. A number of these CD36 ligands elicit the transduction of intracellular signals involved in cell activation and internalization of bound ligands. The engagement of CD36 possibly activates three cytosolic protein tyrosine kinases that are presumably associated with the C- terminal cytoplasmic tail of CD36. However, the mechanisms by which CD36 functions in ligand binding and signal transduction are poorly understood. In the present study, a membrane-bound and a truncated soluble form of CD36 were expressed in HeLa cells and analyzed by velocity-gradient centrifugation and chemical cross-linking. We show that membrane CD36 exists predominantly as a monomer but a homo- dimeric form is also found. In contrast, soluble CD36 sedimented in sucrose gradient as a monomer. However, when incubated with thrombospondin, the membrane form of CD36 predominantly sedimented as a dimer whereas soluble CD36 was monomeric. This study shows that thrombospondin has the ability to induce dimerization of CD36 and may be implicated in the signal transduction capacity of this adhesion molecule.
2
Tandon NN,
Kralisz U,
Jamieson GA.
Identification of glycoprotein IV (CD36) as a primary receptor for platelet-collagen adhesion. J Biol Chem 1989; 264: 7576-7583
4
Savill J,
Hogg N,
Ren Y,
Haslett C.
Thrombospondin cooperates with CD36 and the vitronectin receptor in macrophage recognition of neutrophils undergoing apoptosis. J Clin Invest 1992; 90: 1513-1522
5
Endemann G,
Stanton LW,
Madden KS,
Bryant CM,
White RT,
Protter AA.
CD36 is a receptor for oxidized low density lipoprotein. J Biol Chem 1993; 268: 11811-11816
6
Abumrad NA,
El-Maghrabi MR,
Amri E,
Lopez E,
Grimaldi PA.
Cloning of a rat adipocyte membrane protein implicated in binding or transport of long-chain fatty acids that is induced during preadipocyte differentiation- homology with human CD36. J Biol Chem 1993; 268: 17665-17668
7
Aiken ML,
Ginsberg MH,
Byers-Ward V,
Plow EF.
Effects of OKM5, a monoclonal antibody to glycoprotein IV, on platelet aggregation and thrombospondin surface expression. Blood 1990; 76: 2501-2509
8
Alessio M,
Greco NJ,
Primo L,
Ghigo D,
Bosia A,
Tandon NN,
Ocken-house CF,
Jamieson GA,
Malavasi F.
Platelet activation and inhibition of malarial cytoadherence by the anti-CD36 IgM monoclonal antibody NL07. Blood 1993; 82: 3637-3647
9
Ockenhouse CF,
Magowan C,
Chulay JD.
Activation of monocytes and platelets by monoclonal antibodies or malaria-infected erythrocytes binding to the CD36 surface receptor in vitro. J Clin Invest 1989; 84: 468-475
10
Schüiiepp BJ,
Pfister H,
Clemetson KJ,
Silverstein RL,
Jungi TW.
CD36-mediated signal transduction in human monocytes by anti-CD36 antibodies but not by anti-thrombospondin antibodies recognizing cell membrane-bound thrombospondin. Biochem Biophys Res Commun 1991; 175: 263-270
11
Huang MM,
Bolen JB,
Barnwell JW,
Shattil SJ,
Brugge JS.
Membrane glycoprotein IV (CD36) is physically associated with the Fyn, Lyn, and Yes protein-tyrosine kinases in human platelets. Proc Natl Acad Sci USA 1991; 88: 7844-7848
12
Pearce SFA,
Wu J,
Silverstein RL.
A carboxy terminal truncation mutant of CD36 is secreted and binds thrombospondin: evidence for a single transmembrane domain. Blood 1994; 84: 384-389
14
McGregor JL,
Catimel B,
Parmentier S,
Clezardin P,
Dechavanne M,
Leung LLK.
Rapid purification and partial characterization of human platelet glycoprotein Illb-Interaction with thrombospondin and its role in platelet aggregation. J Biol Chem 1989; 264: 501-506
15
Daviet L,
Buckland R,
Puente NavazoMD,
McGregor L.
Identification of an immunodominant, functional domain on human CD36 using human- mouse chimeric proteins and homologue replacement mutagenesis. Biochem J 1995; 305: 221-224
18
Malvoisin E,
Wild TF.
Analysis of the human immunodeficiency virus type 1 envelope protein interaction with the CD4 host cell receptor. J Gen Virol 1994; 75: 839-847
20
Silverstein RL,
Baird M,
Lo SK,
Yesner LM.
Sense and antisense cDNA transfection of CD36 (glycoprotein IV) in melanoma cells. Role of CD36 as a thrombospondin receptor. J Biol Chem 1992; 267: 16607-16612
21
Yarden Y,
Schlessinger J.
Self-phosphorylation of epidermal growth factor receptor: evidence for a model of intermolecular allosteric activation. Biochemistry 1987; 26: 1434-1442
22
Reilly PL,
Woska Jr JR,
Jeanfavre DD,
McNally E,
Rothlein R,
Bormann BJ.
The native structure of Intercellular Adhesion Molecule-1 (ICAM-1) is a dimer-Correlation with binding to LFA-1. J Immunol 1995; 155: 529-532
26
Li WX,
Howard RJ,
Leung LLK.
Identification of SVTCG in thrombospondin as the conformation-dependant, high affinity binding site for its receptor, CD36. J Biol Chem 1993; 268: 16179-16184
29
Rhinehart-Jones T,
Greenwalt DE.
A detergent-sensitive 113-kDa con- former/complex of CD36 exists on the platelet surface. Arch Biochem Biophys 1996; 326: 115-118