Our program will focus on the molecular mechanisms of oncogenesis by two complementary groups of transforming proteins. The first group consists of intranuclear proteins that regulate growth properties of cells, such as immortalization and serum requirements, and alter transcriptional patterns of cells by unknown mechanisms. Projects 2, 4, 5, and 6 will investigate important representatives of these proteins. The second group consists of membrane-associated transforming proteins that have protein kinase and receptor-like activities. Projects 1 and 3 will investigate two of these transforming proteins directly, and Project 7 will deal with the receptor problem using well-characterized viral systems. An increased understanding of the activities of the intranuclear and membrane-associated transforming proteins may establish a common link between these functional groups. The specific topics of these related studies are: Project 1 - Investigations of the functional activity of the cellular src gene, Project 2 - Target cell selection by the myc gene of avian acute leukemia viruses, Project 3 - Mechanisms of action of the erb-B oncogene, Project 4 - Cis and Trans regulation of adenovirus transcription, Project 5 - In vitro studies of adeno-associated virus excision and DNA replication, Project 6 - Characterization of the SV40 early promoter-operator region, and Project 7 - Characterization of the poliovirus and adenovirus receptors.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Special Emphasis Panel (SRC (E1))
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State University New York Stony Brook
Schools of Medicine
Stony Brook
United States
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Feres, Kimberly J; Hayman, Michael J (2010) RON-expressing MCF-10A breast epithelial cells exhibit alterations of hyaluronan expression, promoting RON-mediated early adhesion events. Biochem Biophys Res Commun 391:1604-9
Feres, K J; Ischenko, I; Hayman, M J (2009) The RON receptor tyrosine kinase promotes MSP-independent cell spreading and survival in breast epithelial cells. Oncogene 28:279-88
Yoo, Jae Cheal; Hayman, Michael J (2007) Annexin II binds to SHP2 and this interaction is regulated by HSP70 levels. Biochem Biophys Res Commun 356:906-11
Tartaglia, Marco; Pennacchio, Len A; Zhao, Chen et al. (2007) Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome. Nat Genet 39:75-9
Reich, Nancy C (2007) STAT dynamics. Cytokine Growth Factor Rev 18:511-8
Yondola, Mark A; Hearing, Patrick (2007) The adenovirus E4 ORF3 protein binds and reorganizes the TRIM family member transcriptional intermediary factor 1 alpha. J Virol 81:4264-71
Ullman, Amanda J; Reich, Nancy C; Hearing, Patrick (2007) Adenovirus E4 ORF3 protein inhibits the interferon-mediated antiviral response. J Virol 81:4744-52
Zhao, Chen; Du, Guangwei; Skowronek, Karl et al. (2007) Phospholipase D2-generated phosphatidic acid couples EGFR stimulation to Ras activation by Sos. Nat Cell Biol 9:706-12
Kim, Hong Joo; Taylor, Laura J; Bar-Sagi, Dafna (2007) Spatial regulation of EGFR signaling by Sprouty2. Curr Biol 17:455-61
Merritt, Rebecca; Hayman, Michael J; Agazie, Yehenew M (2006) Mutation of Thr466 in SHP2 abolishes its phosphatase activity, but provides a new substrate-trapping mutant. Biochim Biophys Acta 1763:45-56

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