Abstract

This application focuses on the mechanisms of EGF receptor signaling. The investigator has recently identified a new protein ZPR1, which binds to the tyrosine kinase region of the EGF receptor. EGF binding to its receptor decreases the binding of ZPR1 thus releasing this protein from the EGF receptor following receptor activation. The investigator wishes to determine the functional significance and mechanisms of ZPR1 binding to the EGF receptor signaling pathway.
Three aims are proposed. In the first aim, the investigator will determine the role of ZPR1 in EGF receptor signal transduction. In the second aim, the investigator will attempt to identify target molecules that interact with ZPR1. In the third specific aim, the investigator will determine ZPR1 function using genetic analysis in yeast.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA058396-06
Application #
2654104
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Program Officer
Spalholz, Barbara A
Project Start
1993-02-01
Project End
2002-01-31
Budget Start
1998-02-01
Budget End
1999-01-31
Support Year
6
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of Massachusetts Medical School Worcester
Department
Biochemistry
Type
Schools of Medicine
DUNS #
660735098
City
Worcester
State
MA
Country
United States
Zip Code
01655

  Publications

Diehl, N L; Enslen, H; Fortner, K A et al. (2000) Activation of the p38 mitogen-activated protein kinase pathway arrests cell cycle progression and differentiation of immature thymocytes in vivo. J Exp Med 191:321-34
Weiss, L; Whitmarsh, A J; Yang, D D et al. (2000) Regulation of c-Jun NH(2)-terminal kinase (Jnk) gene expression during T cell activation. J Exp Med 191:139-46
Lu, H T; Yang, D D; Wysk, M et al. (1999) Defective IL-12 production in mitogen-activated protein (MAP) kinase kinase 3 (Mkk3)-deficient mice. EMBO J 18:1845-57
Gangwani, L; Mikrut, M; Galcheva-Gargova, Z et al. (1998) Interaction of ZPR1 with translation elongation factor-1alpha in proliferating cells. J Cell Biol 143:1471-84
Galcheva-Gargova, Z; Gangwani, L; Konstantinov, K N et al. (1998) The cytoplasmic zinc finger protein ZPR1 accumulates in the nucleolus of proliferating cells. Mol Biol Cell 9:2963-71
Whitmarsh, A J; Yang, S H; Su, M S et al. (1997) Role of p38 and JNK mitogen-activated protein kinases in the activation of ternary complex factors. Mol Cell Biol 17:2360-71
Chow, C W; Rincon, M; Cavanagh, J et al. (1997) Nuclear accumulation of NFAT4 opposed by the JNK signal transduction pathway. Science 278:1638-41
Fuchs, S Y; Dolan, L; Davis, R J et al. (1996) Phosphorylation-dependent targeting of c-Jun ubiquitination by Jun N-kinase. Oncogene 13:1531-5
Raingeaud, J; Whitmarsh, A J; Barrett, T et al. (1996) MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway. Mol Cell Biol 16:1247-55
Galcheva-Gargova, Z; Konstantinov, K N; Wu, I H et al. (1996) Binding of zinc finger protein ZPR1 to the epidermal growth factor receptor. Science 272:1797-802

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