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Study of new signaling pathways involving grb2/grb3-3 isoforms

Objective



Research objectives and content
Grb2 and Grb3-3 are two isoforms involved in cell proliferation, differentiation and apoptosis. To identify proteins interacting with these adaptor molecules, I performed a two-hybrid screen with a Iymphoid cell cDNA library using Grb3-3 as bait. To start, I propose to characterize structurally and functionally two of the positive clones: human PTTG, a new member of a family of proteins which are transforming in fibroblasts, and Brol-like, which either is a substrate for or a member of MEK kineses. First I will confirm the Grb/PITG interaction in vitro and in vivo (by GST fusion proteins and coimmunoprecipitations, respectively), and I will determine the domains of proteins involved in the interaction. I will study if human PTTG is transforming by transfecting fibroblasts and by their ability to produce tumors in nude mice. I wDI also study the funcdon of PTTG by determining the expression of the gene in embryonic development and adult tissues, the subcellular localization of protein, the regulation of gene expression in normal cells and by searching for interacting proteins (two hybrid system and phage display approach). Finally, I will isolate and caracterizate the brol-like gene, as a potential gene involved in Ras-MAPK pathway.
Training content (objective, benefit and expected impact)
I had the great oportunity to complete a solid multidisciplinary training in my postdoctoral period. On my return tO Seville I am eager to contribute to the formation of young scientists. Furthermore, the host laboratory has significant experience in the molecular basis of intracellular traffic which will largely benefit my project. Links with industry / industrial relevance (22)
This project is the basis for the collaboration of the Molecular Oncology laboratory of Rhone Poulenc-Rorer with the laboratory in Seville.

Funding Scheme

RGI - Research grants (individual fellowships)

Coordinator

UNIVERSIDAD DE SEVILLA
Address
6,Av. Reina Mercedes 6
41012 Sevilla
Spain