Normal lymphocyte function is highly dependent on a variety of cell surface receptors that mediate cell-cell adhesion, and transmit contact-dependent activation signals to the cellular interior. The project described focuses on three adhesion-dependent responses in T and B cells. CD22 is a sialic acid-binding receptor that recognizes sIgM and CD45. This project will examine the role of sialylation of CD22 itself in the ligand-binding activity of this receptor. Wild-type and mutant forms of CD22 will be introduced into CD22 nullizygous B cells to determine whether alterations in the sialylation of the extracellular domain augments or interferes with the function of CD22. The investigator has identified a novel, inducible ligand for CD5 on activated B cells, and has shown that CD5 glycosylation regulates CD5 binding to this ligand. The investigator now plans to study the glycosylation of CD5 in detail, and to clone the novel CD5 ligand. Two cDNAs encoding putative ligands for the L-Selectin cytoplasmic domain have been cloned, and the objective of the third aim of this project is to characterize the cDNAs, and to examine their roles in L-Selectin-mediated adhesion and rolling.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM048614-04
Application #
2468099
Study Section
Experimental Immunology Study Section (EI)
Project Start
1994-08-01
Project End
2001-11-30
Budget Start
1997-12-01
Budget End
1998-11-30
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Hampton, Mark B; Stamenkovic, Ivan; Winterbourn, Christine C (2002) Interaction with substrate sensitises caspase-3 to inactivation by hydrogen peroxide. FEBS Lett 517:229-32
Fiore, Emilio; Fusco, Carlo; Romero, Pedro et al. (2002) Matrix metalloproteinase 9 (MMP-9/gelatinase B) proteolytically cleaves ICAM-1 and participates in tumor cell resistance to natural killer cell-mediated cytotoxicity. Oncogene 21:5213-23
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Yu, Q; Stamenkovic, I (2000) Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes Dev 14:163-76
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Biancone, L; Cantaluppi, V; Boccellino, M et al. (1999) Activation of CD40 favors the growth and vascularization of Kaposi's sarcoma. J Immunol 163:6201-8
Biancone, L; Stamenkovic, I; Cantaluppi, V et al. (1999) Expression of L-selectin ligands by transformed endothelial cells enhances T cell-mediated rejection. J Immunol 162:5263-9
Yu, Q; Stamenkovic, I (1999) Localization of matrix metalloproteinase 9 to the cell surface provides a mechanism for CD44-mediated tumor invasion. Genes Dev 13:35-48
Barnes, Y C; Skelton, T P; Stamenkovic, I et al. (1999) Sialylation of the sialic acid binding lectin sialoadhesin regulates its ability to mediate cell adhesion. Blood 93:1245-52

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