Abstract

The central goal of this proposal is to use recently obtained monoclonal antibodies which specifically bind to the protein portion of the nerve growth factor (NGF) receptor to further our understanding of the regulation by NGF of neural development and differentiation. Monoclonal antibodies will be used for immunoperoxidase staining of tissue sections to determine the cellular distribution of the NGF receptor. Experiments utilizing monoclonal antibodies for immunoprecipitation will better define the biochemical nature of the NGF receptor. The NGF receptor will be isolated by immunoaffinity chromatography and used for amino acid sequencing and as an immunogen for the preparation of new monoclonal and polyclonal reagents. Antisera will also be prepared against synthetic peptides based on the amino acid sequence of the receptor. A nucleic acid clone of the NGF receptor will be obtained by transfection of murine cells with human DNA using anti-receptor monoclonal antibodies to screen the resulting colonies. Such a DNA clone will allow complete sequencing of the receptor as well as studies of the function of the receptor, the regulation of its expression and its involvement in neural-related genetic diseases.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS021716-02
Application #
3403180
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1985-09-01
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Wistar Institute
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Weatherbee, Jessica L; Kraus, Jean-Louis; Ross, Alonzo H (2016) ER stress in temozolomide-treated glioblastomas interferes with DNA repair and induces apoptosis. Oncotarget 7:43820-43834
Heinrich, Frank; Chakravarthy, Srinivas; Nanda, Hirsh et al. (2015) The PTEN Tumor Suppressor Forms Homodimers in Solution. Structure 23:1952-1957
Harishchandra, Rakesh K; Neumann, Brittany M; Gericke, Arne et al. (2015) Biophysical methods for the characterization of PTEN/lipid bilayer interactions. Methods 77-78:125-35
Ramirez, Yulian P; Mladek, Ann C; Phillips, Roger M et al. (2015) Evaluation of novel imidazotetrazine analogues designed to overcome temozolomide resistance and glioblastoma regrowth. Mol Cancer Ther 14:111-9
Karpel-Massler, Georg; Shu, Chang; Chau, Lily et al. (2015) Combined inhibition of Bcl-2/Bcl-xL and Usp9X/Bag3 overcomes apoptotic resistance in glioblastoma in vitro and in vivo. Oncotarget 6:14507-21
Pareja, Fresia; Macleod, David; Shu, Chang et al. (2014) PI3K and Bcl-2 inhibition primes glioblastoma cells to apoptosis through downregulation of Mcl-1 and Phospho-BAD. Mol Cancer Res 12:987-1001
Jiang, Zhiping; Redfern, Roberta E; Isler, Yasmin et al. (2014) Cholesterol stabilizes fluid phosphoinositide domains. Chem Phys Lipids 182:52-61
Ramirez, Yulian P; Weatherbee, Jessica L; Wheelhouse, Richard T et al. (2013) Glioblastoma multiforme therapy and mechanisms of resistance. Pharmaceuticals (Basel) 6:1475-506
Gericke, Arne; Leslie, Nicholas R; Lösche, Mathias et al. (2013) PtdIns(4,5)P2-mediated cell signaling: emerging principles and PTEN as a paradigm for regulatory mechanism. Adv Exp Med Biol 991:85-104
Shenoy, Siddharth; Shekhar, Prabhanshu; Heinrich, Frank et al. (2012) Membrane association of the PTEN tumor suppressor: molecular details of the protein-membrane complex from SPR binding studies and neutron reflection. PLoS One 7:e32591

Showing the most recent 10 out of 64 publications