This application aims to study the mechanisms involved in alterations in cell adhesion induced by ras related GTB binding protein R-ras. They hope to identify novel components leading to integrin activation and the subsequent search for their de-regulation in tumors.
The specific aims are the following: 1) to identify which residues within R-ras code for sequences in cell adhesion. Chimeric mutants between R-ras and H-ras will be used. 2) The role of various effectors of R-ras mediating cell adhesion functions will be delineated. A panel of R-ras functional mutants with varying abilities to induce cell adhesion will be examined for their ability to interact with ras effectors. 3) Specific aim #3 will assess the role of R-ras in modulating cell adhesion by altering the downstream events mediated by ras such as the ras/raf MAP kinase pathway. In this specific aim the biologic consequences of crossed top between R-ras and ras will be explored with respect to regulating cell adhesion during cell division. In summary this proposal addresses some of the important and timely issues concerning the mechanisms by which ras related G proteins confer signaling specificity in controlling vital biologic functions such as cell adhesion.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29CA078509-01
Application #
2677875
Study Section
Pathology B Study Section (PTHB)
Program Officer
Mohla, Suresh
Project Start
1998-07-01
Project End
2003-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
114400633
City
New York
State
NY
Country
United States
Zip Code
10029
Yan, Xiaocai; Yan, Mingfei; Guo, Yihe et al. (2015) R-Ras Regulates Murine T Cell Migration and Intercellular Adhesion Molecule-1 Binding. PLoS One 10:e0145218
Singh, Gobind; Hashimoto, Daigo; Yan, Xiaocai et al. (2012) R-Ras is required for murine dendritic cell maturation and CD4+ T-cell priming. Blood 119:1693-701
Nunez Rodriguez, Nelson; Lee, Ivy N L; Banno, Asoka et al. (2006) Characterization of R-ras3/m-ras null mice reveals a potential role in trophic factor signaling. Mol Cell Biol 26:7145-54
Kimmelman, Alec C; Qiao, Rui F; Narla, Goutham et al. (2004) Suppression of glioblastoma tumorigenicity by the Kruppel-like transcription factor KLF6. Oncogene 23:5077-83
Kimmelman, Alec C; Nunez Rodriguez, Nelson; Chan, Andrew M-L (2002) R-Ras3/M-Ras induces neuronal differentiation of PC12 cells through cell-type-specific activation of the mitogen-activated protein kinase cascade. Mol Cell Biol 22:5946-61
Tolkacheva, T; Boddapati, M; Sanfiz, A et al. (2001) Regulation of PTEN binding to MAGI-2 by two putative phosphorylation sites at threonine 382 and 383. Cancer Res 61:4985-9
Tolkacheva, T; Chan, A M (2000) Inhibition of H-Ras transformation by the PTEN/MMAC1/TEP1 tumor suppressor gene. Oncogene 19:680-9
Kimmelman, A C; Osada, M; Chan, A M (2000) R-Ras3, a brain-specific Ras-related protein, activates Akt and promotes cell survival in PC12 cells. Oncogene 19:2014-22
Osada, M; Tolkacheva, T; Li, W et al. (1999) Differential roles of Akt, Rac, and Ral in R-Ras-mediated cellular transformation, adhesion, and survival. Mol Cell Biol 19:6333-44