T lymphocytes play a critical role in immune responses to both extracellular pathogens and transformed cells. Regulation of lymphocyte proliferation and differentiation is a multistep process that integrates a cascade of activation signals. The molecular mechanisms that link primary activation events occurring at the plasma membrane to alterations in the pattern and function of cytoplasmic and nuclear elements remain poorly understood. Recent data has focused attention on the role of glycosylated-phosphatidylinositol (GPI) molecules as key elements in the generation of intracellular messenger molecules and regulation of cellular proliferation. GPI molecules serve important dual functions in eukaryotic cells as membrane anchors for proteins and as precursors to insulin sensitive pharmacologically active inositolphosphoglycans (IPG). Both forms of GPI are utilized in the regulation of T cell growth. Aggregation of GPI anchored proteins such as Thy-1 can initiate a mitogenic response, and free GPI has been proposed as a precursor to second messengers of interleukin 2 and insulin action. The goal of this proposal is to elucidate the biochemical basis and molecular mechanisms of GPI controlled signaling processes during the early phases of T cell proliferation.
The specific aims are: 1) Analysis of the relationship between heterogeneous GPI structure and function, 2) Examination of GPI structure-function relationships using antibody probes, and 3) Examination of the roles of gpi molecules in T cell signalling.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM042626-03
Application #
3301346
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1991-04-01
Project End
1995-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104