Abstract

These studies are designed in part to identify and characterize the crucial polypeptide substrates of viral transforming proteins which possess tyrosine protein kinase activity. Novel substrates will be sought by """"""""Western Blotting"""""""" using anti-phosphotyrosine antibodies. Since there are indications that the phosphorylation of many of the substrates of the viral protein kinases does not contribute materially to cellular transformation, advantage will be taken of mutants of Rous sarcoma virus which encode a non- fatty acylated transforming protein. These mutant proteins posses undimished protein kinase activity but cannot transform cells. The small subset of the substrates of the wild-type protein which do not undergo phosphorylation in cells infected with these mutants will be identified and studied. In addition, a variety of immune reagents--tumor sera and sera produced by immunization with proteins expressed in bacteria-- will be prepared and used to proto-oncogenes. The properties and structure of these proteins will be determined and the cells in which they are expressed will be identified. The effect of growth factors on the protein kinase activity and the phosphorylation of these cellular proteins will be examined.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA017289-16
Application #
3164643
Study Section
Virology Study Section (VR)
Project Start
1979-01-01
Project End
1992-06-30
Budget Start
1991-01-01
Budget End
1992-06-30
Support Year
16
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Salk Institute for Biological Studies
Department
Type
DUNS #
005436803
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

Schulte, Roberta J; Sefton, Bartholomew M (2003) Inhibition of the activity of SRC and Abl tyrosine protein kinases by the binding of the Wiskott-Aldrich syndrome protein. Biochemistry 42:9424-30
Kjellen, Peter; Amdjadi, Kambiz; Lund, Troy C et al. (2002) The herpesvirus saimiri tip484 and tip488 proteins both stimulate lck tyrosine protein kinase activity in vivo and in vitro. Virology 297:281-8
Amdjadi, K; Sefton, B M (2000) Ultraviolet light-induced stimulation of the JNK mitogen-activated protein kinase in the absence of src family tyrosine kinase activation. J Biol Chem 275:22520-5
Yurchak, L K; Hardwick, J S; Amrein, K et al. (1996) Stimulation of phosphorylation of Tyr394 by hydrogen peroxide reactivates biologically inactive, non-membrane-bound forms of Lck. J Biol Chem 271:12549-54
Schulte, R J; Campbell, M A; Fischer, W H et al. (1994) Tyrosine phosphorylation of VCP, the mammalian homologue of the Saccharomyces cerevisiae CDC48 protein, is unusually sensitive to stimulation by sodium vanadate and hydrogen peroxide. J Immunol 153:5465-72
Taddie, J A; Hurley, T R; Hardwick, B S et al. (1994) Activation of B- and T-cells by the cytoplasmic domains of the B-cell antigen receptor proteins Ig-alpha and Ig-beta. J Biol Chem 269:13529-35
Taddie, J A; Hurley, T R; Sefton, B M (1994) B-cell activation by wild type and mutant Ig-beta cytoplasmic domains. Adv Exp Med Biol 365:23-34
Schulte, R J; Campbell, M A; Fischer, W H et al. (1992) Tyrosine phosphorylation of CD22 during B cell activation. Science 258:1001-4
Campbell, M A; Sefton, B M (1992) Association between B-lymphocyte membrane immunoglobulin and multiple members of the Src family of protein tyrosine kinases. Mol Cell Biol 12:2315-21
Luo, K; Hurley, T R; Sefton, B M (1990) Transfer of proteins to membranes facilitates both cyanogen bromide cleavage and two-dimensional proteolytic mapping. Oncogene 5:921-3

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