The overall objective is to investigate the structure and function of gag-mos and env-mos proteins encoded by Moloney murine sarcoma virus (MuSV) for the purpose of elucidating the molecular mechanism by which v-mos products produce transformation in viral infected cells. Efforts will be made to compare the transforming potential of the gag-mos proteins to env-mos proteins of Maloney MuSV. Overall, these studies will yield valuable and significant information on the mechanism of transformation by the activated mos gene. It is of special interest that a ts gag-mos gene mutant will be used in these studies. Such mutants are important tools in determining the function of oncogene products. Of prime importance is our discovery that P85gag-mos and p37env-mos have an associated protein kinase activity. Using anti-v-mos peptide sera, we have detected a 55k normal cellular nuclear protein (P55) whose expression is specifically inhibited during acute infection by MuSV.
The Specific Aims i nclude: 1) Purify the protein kinase associated with P85gag-mos and/or p37env-mos; 2) Determine whether the bacterially expressed partially purified env-mos protein (50% pure) active in transformation of NIH 3T3 cells following transfection, has protein kinase activity. This work is being done in collaboration with Dr. Arun Seth of George Vande Woude's group at the Frederick Cancer Center; 3) Determine the location of the phosphorylation sites within gag-mos and env-mos proteins and identify their phosphopeptides; 4) Characterize the structure of the P55 protein by peptide mapping and limited amino acid sequencing; 5) Determine the sites of phosphorylation of P55 by the v-mos serine kinase and verify the presence of phosphoserine; 6) Clone the cellular gene for P55 by recombinant DNA techniques; 7) Identify other possible cellular targets for v-mos proteins; 8) Search for c-mos proteins using synthetic peptide antisera; 9) In collaboration with Dr. Steve Reed of the University of California at Santa Barbara, prepare site directed mutants of the v-mos gene coding for p37env-mos.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA045125-03
Application #
3188106
Study Section
Experimental Virology Study Section (EVR)
Project Start
1986-09-30
Project End
1990-04-30
Budget Start
1988-05-01
Budget End
1990-04-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Type
Hospitals
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030
Pham, C D; Vuyyuru, V B; Yang, Y et al. (1999) Evidence for an important role of serine 16 and its phosphorylation in the stabilization of c-Mos. Oncogene 18:4287-94
Liu, H; Vuyyuru, V B; Pham, C D et al. (1999) Evidence of an interaction between Mos and Hsp70: a role of the Mos residue serine 3 in mediating Hsp70 association. Oncogene 18:3461-70
Yang, Y; Pham, C D; Vuyyuru, V B et al. (1998) Evidence of a functional interaction between serine 3 and serine 25 Mos phosphorylation sites. A dominant inhibitory role of serine 25 phosphorylation on Mos protein kinase. J Biol Chem 273:15946-53
Yang, Y; Pham, C D; Arlinghaus, R B et al. (1998) Elevated level of cyclin D1 in mos-transformed cells. Int J Oncol 12:1199-202
Singh, B; Arlinghaus, R B (1997) Mos and the cell cycle. Prog Cell Cycle Res 3:251-9
Gao, C; Arlinghaus, R B; Singh, B (1996) Further characterization of the c-mos transcript and its cell cycle specific expression in NIH3T3 cells. Oncogene 12:1571-6
Yang, Y; Herrmann, C H; Arlinghaus, R B et al. (1996) Inhibition of v-Mos kinase activity by protein kinase A. Mol Cell Biol 16:800-9
Pham, C D; Arlinghaus, R B; Zheng, C F et al. (1995) Characterization of MEK1 phosphorylation by the v-Mos protein. Oncogene 10:1683-8
Bai, W; Arlinghaus, R B; Singh, B (1993) Association of v-Mos with soluble vimentin in vitro and in transformed cells. Oncogene 8:2207-12
Bai, W; Singh, B; Yang, Y et al. (1992) Evidence for interaction between v-Mos and a p34cdc2 isoform, p35cdk. Oncogene 7:1757-63

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