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.
