Studies of the metabolism of the epidermal growth factor (EGF) receptor and the erbB protein will continue. These studies should contribute to the understanding of some of the mechanisms involved in regulation of cell division in higher organisms. The relationship between EGF receptor and erbB protein mediated mitogenesis and phosphorylation of proteins on tyrosine residues will be examined using antibodies against these proteins and anti-phosphotyrosine antibodies. The effects of in vivo tyrosine phosphorylation of the EGF receptor and erbB protein on their respective activities will be determined. Anti-phosphotyrosine antibodies will be used to isolate tyrosine phosphorylated proteins from EGF treated cells and avian erythroblastosis virus (AEV) transformed cells. These proteins may play a role in triggering cell division. Particular attention will be paid to the identification of tyrosine phosphorylated membrane proteins and proteins which associate with the tyrosine phosphorylated forms of the EFG receptor and erbB proteins. The mechanism through which tumor promoters attenuate mitogenic signalling of the EGF receptor and erbB protein will be approached. The effects of tumor promoters on tyrosine phosphorylation of proteins will be determined. Cells will be transformed by AEV containing erbB protein mutated at or near threonine 98 (which is phosphorylated in response to tumor promoter treatment of cells). These cells will be assessed for altered responses to tumor promoters. The effects of platelet derived growth factor on EGF receptor function will also be investigated. The metabolism of carboxy terminus truncated erbB protein versus full length carboxy terminus erbB protein will be studied with respect to biosynthesis, turnover, intracellular localization, kinase activity and oncogenicity. Study of the unusual metabolism of the EGF receptor in the MDA-MB-231 human breast cancer cell line will continue with emphasis on characterization EGF receptor containing endosomes from these cells. Phosphorylation of the EGF receptor will also be more thoroughly examined in these cells. Initial characterization of the c-erbB protein from Drosophila will be begun using antisera prepared against recombinant protein. Analysis of a M=100,000 Drosophila growth factor binding protein will continue. Structural comparison of the v-erbA and c-erbA proteins will be performed, again, using antiserum prepared against recombinant protein.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA037754-06
Application #
3175550
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1985-05-01
Project End
1990-06-30
Budget Start
1990-05-01
Budget End
1990-06-30
Support Year
6
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Rockefeller University
Department
Type
Other Domestic Higher Education
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
Zhu, G; Decker, S J; Mayer, B J et al. (1993) Direct analysis of the binding of the abl Src homology 2 domain to the activated epidermal growth factor receptor. J Biol Chem 268:1775-9
Decker, S J (1993) Transmembrane signaling by epidermal growth factor receptors lacking autophosphorylation sites. J Biol Chem 268:9176-9
Decker, S J; Alexander, C; Habib, T (1992) Epidermal growth factor (EGF)-stimulated tyrosine phosphorylation and EGF receptor degradation in cells expressing EGF receptors truncated at residue 973. J Biol Chem 267:1104-8
Ohmichi, M; Decker, S J; Pang, L et al. (1992) Inhibition of the cellular actions of nerve growth factor by staurosporine and K252A results from the attenuation of the activity of the trk tyrosine kinase. Biochemistry 31:4034-9
Zhu, G; Decker, S J; Saltiel, A R (1992) Direct analysis of the binding of Src-homology 2 domains of phospholipase C to the activated epidermal growth factor receptor. Proc Natl Acad Sci U S A 89:9559-63
Ohmichi, M; Pang, L; Decker, S J et al. (1992) Nerve growth factor stimulates the activities of the raf-1 and the mitogen-activated protein kinases via the trk protooncogene. J Biol Chem 267:14604-10
Ohmichi, M; Decker, S J; Saltiel, A R (1992) Nerve growth factor stimulates the tyrosine phosphorylation of a 38-kDa protein that specifically associates with the src homology domain of phospholipase C-gamma 1. J Biol Chem 267:21601-6
Ohmichi, M; Decker, S J; Saltiel, A R (1992) Activation of phosphatidylinositol-3 kinase by nerve growth factor involves indirect coupling of the trk proto-oncogene with src homology 2 domains. Neuron 9:769-77
Brott, B K; Decker, S; Shafer, J et al. (1991) GTPase-activating protein interactions with the viral and cellular Src kinases. Proc Natl Acad Sci U S A 88:755-9
Ohmichi, M; Decker, S J; Pang, L et al. (1991) Nerve growth factor binds to the 140 kd trk proto-oncogene product and stimulates its association with the src homology domain of phospholipase C gamma 1. Biochem Biophys Res Commun 179:217-23

Showing the most recent 10 out of 24 publications