Abstract

The proposed research will identify at the molecular level the pathways utilized by the PRL-R in regulating the growth of normal and malignant T lymphocytes. First, the structural-functional determinants of the transmembrane and intracytoplasmic domains of the PRL-R will be mapped through the transfection of chimeric receptors into T cell lines. These chimeric receptors will be composed of the extracellular domain of the granulocyte-macrophage colony stimulating factor receptor (GM-CSF-R) and deletional mutants of the intracellular domain of the PRL-R. The T-cell clones containing the chimeric receptors will then be used to study the contributions of the intracellular and transmembrane domains of the PRL-R to T lymphocyte proliferation and the nuclear translocation of PRL. Second, PRL-R binding proteins will be identified by coimmunop- recipitation studies, and their ability to bind to the mutant chimeric receptors will be examined.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29AI033510-01
Application #
3456274
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1993-01-01
Project End
1997-12-31
Budget Start
1993-01-01
Budget End
1993-12-31
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Clevenger, C V; Freier, D O; Kline, J B (1998) Prolactin receptor signal transduction in cells of the immune system. J Endocrinol 157:187-97
Chang, W P; Ye, Y; Clevenger, C V (1998) Stoichiometric structure-function analysis of the prolactin receptor signaling domain by receptor chimeras. Mol Cell Biol 18:896-905
Clevenger, C V; Thickman, K; Ngo, W et al. (1997) Role of Bag-1 in the survival and proliferation of the cytokine-dependent lymphocyte lines, Ba/F3 and Nb2. Mol Endocrinol 11:608-18
Reynolds, C; Montone, K T; Powell, C M et al. (1997) Expression of prolactin and its receptor in human breast carcinoma. Endocrinology 138:5555-60
Clevenger, C V; Plank, T L (1997) Prolactin as an autocrine/paracrine factor in breast tissue. J Mammary Gland Biol Neoplasia 2:59-68
Chang, W P; Clevenger, C V (1996) Modulation of growth factor receptor function by isoform heterodimerization. Proc Natl Acad Sci U S A 93:5947-52
Luger, S M; Ratajczak, J; Ratajczak, M Z et al. (1996) A functional analysis of protooncogene Vav's role in adult human hematopoiesis. Blood 87:1326-34
Clevenger, C V; Ngo, W; Sokol, D L et al. (1995) Vav is necessary for prolactin-stimulated proliferation and is translocated into the nucleus of a T-cell line. J Biol Chem 270:13246-53
Clevenger, C V; Chang, W P; Ngo, W et al. (1995) Expression of prolactin and prolactin receptor in human breast carcinoma. Evidence for an autocrine/paracrine loop. Am J Pathol 146:695-705
Clevenger, C V; Medaglia, M V (1994) The protein tyrosine kinase P59fyn is associated with prolactin (PRL) receptor and is activated by PRL stimulation of T-lymphocytes. Mol Endocrinol 8:674-81

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