IGE BINDING PROTEIN--A MULTIFUNCTIONAL ANIMAL LECTIN

  • Liu, Fu-Tong, (PI)

Project: Research project

Description

The focus of this project is on IgE-binding protein (epsilon-BP) with
emphasis on its modulatory role on mast cell functions. Epsilon-BP is a
31,000 Mr protein identified in rat basophilic leukemia (RBL) cells and
is now known as soluble lectin designated with different names by other
laboratories and appears to have multiple functions. The protein has
wide tissue distribution, is found on the cell surface and also secreted
under certain conditions. Epsilon-BP has specificity for distinct
oligosaccharide structures that have a terminal galactose not masked by
sialic acids and it functions at least bivalently. In addition to
binding IgE, epsilon-BP binds to surfaces of various cell types,
including mast cells. First, the molecular basis for multivalency of epsilon-BP will be
elucidated. We have evidence that epsilon-BP has a tendency to
self-associate through intermolecular interactions involving the amino--
terminal domain, resulting in dimers or oligomers. This property of
epsilon-BP will be further investigated, including equilibrium
ultracentrifugation analysis and binding to lactosyl-Sepharose 4B
containing varying densities of lactose. Another explanation for
bivalency of epsilon-BP is the formation of a dimer through an
inter-molecular disulfide linkage. The molecular mechanism for the
covalent dimerization of epsilon-BP will be investigated. Second, cell surface glycoprotein ligands for epsilon-BP will be
identified. Preliminary studies indicate that epsilon-BP is attached to
glycoconjugates on the surface of mast cells and only a small number of
different glycoproteins species on RBL cell surface are recognized by
epsilon-BP. Significantly, one of these glycoproteins is the high
affinity IgE receptor (Fc-epsilon-RI). We will focus on isolation and
characterization of another epsilon-BP-reactive Mr 150,00 glycoprotein.
We will then investigate possible variation in epsilon-BP recognition of
FC-epsilon-RI on mast cells at various differentiation stages or
activation status. Third, the function of epsilon-BP as a multifunctional modulator molecule
will be established. Having demonstrated epsilon-BP's multivalent
property and recognition of cell surface glycoproteins, especially
Fc-epsilon-RI, we propose that this lectin has the potential to modulate
cellular functions of mast cells mediated by these glycoproteins. We
have already shown that epsilon-BP potentiates Fc-epsilon-RI-mediated
mast cell activation. We will further substantiate this modulator role
of epsilon-BP and investigate the mechanism for the observed potentiating
effect.
StatusFinished
Effective start/end date4/1/844/30/10

Funding

  • National Institutes of Health
  • National Institutes of Health: $44,362.00
  • National Institutes of Health
  • National Institutes of Health: $276,259.00
  • National Institutes of Health
  • National Institutes of Health: $297,000.00
  • National Institutes of Health: $75,688.00
  • National Institutes of Health
  • National Institutes of Health: $211,344.00
  • National Institutes of Health: $200,924.00
  • National Institutes of Health: $297,000.00
  • National Institutes of Health: $290,021.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $243,760.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $257,846.00
  • National Institutes of Health: $231,616.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $281,609.00
  • National Institutes of Health

Fingerprint

Galectin 3
Immunoglobulin E
Galectins
Lectins
Staphylococcal Protein A
Innate Immunity
Mast Cells
Gene Expression
IgE Receptors
Apoptosis
Glycoproteins
Growth
Membrane Glycoproteins
Macrophages
Leukemia
Phagosomes
Proteins
Tuberculosis
Phagocytosis
Dimerization

Keywords

  • Medicine(all)
  • Immunology and Microbiology(all)