GLYCOLIPID PROTEIN ANCHORS IN PNH AND THY-1 MUTANTS

  • Rosenberry, Terrone L, (PI)
  • Medof, M. Edward (PI)
  • Medof, M. Edward (PI)
  • Tykocinski, Mark (PI)
  • Tartakoff, Alan (PI)
  • Gray, Wesley (PI)

Project: Research project

Description

Plasma membrane proteins anchored via a glycophospholipid are
of critical importance for a number of metabolic and homeostatic
functions. Moreover, their modulation may result in the ability of
cells to escape immune recognition. The present proposal is
concerned with three such proteins: decay accelerating factor
(DAF), acetylcholinesterase, and Thy-1. The proposal is highly
inter-disciplinary--both from a conceptual and from a technical
point of view--and exploits chemical, cell biological, biochemical,
molecular biological and immunological approaches. The
extensive investigation of the structure of the anchor of
acetylcholinesterase makes use of human red cells; the studies of
Thy-1 focus on a family of five mouse lymphoma mutants which
synthesize Thy-1 but fail to express it on the cell surface,
apparently due to an inability to synthesize its anchor; the studies
of DAF concern fluids, tissues and cultured cells of control
individuals and of individuals suffering from paroxysmal nocturnal
hemoglobinuria (PNH). In this disease, cell surface DAF (and
acetylcholinesterase) are grossly deficient, although precursor
species of DAF are synthesized. The underlying in PNH may,
therefore, be related to those of the Thy-1 negative mutants. The
unifying theme of the proposed research is the structure,
biosynthesis and function(s) of glycophospholipid anchors.
StatusFinished
Effective start/end date9/1/878/31/99

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Glycolipids
Membrane Proteins
Acetylcholinesterase
Phospholipids
Polysaccharides
Phosphatidylinositols
Trypanosomiasis
Phosphoinositide Phospholipase C
Glucosamine
Insulin
Proteins
Deamination
Phospholipases
Hemoglobinuria
CD55 Antigens
Fast Atom Bombardment Mass Spectrometry
Inositol
Cell Extracts
Reticulum
Ethanolamine

ASJC

  • Medicine(all)