'FROM DISCOVERY TO RECOVERY'
GTP-binding proteins of the Ras superfamily (RhoA, Rac, Cdc42, Ras, Rap) are key intermediaries between cell surface receptors and effectors which regulate several cellular functions such as proliferation, differentiation and migration. A hallmark of monomeric GTPases is their ability to dynamically cycle between a GDP-bound inactive to a GTP-bound active form. I have initially focused my attention on the regulation of Rho GTPases (RhoA, Rac, Cdc42) by integrins in human polymorphonuclear neutrophils (PMN). PMN represent an ideal model in which to study regulation of monomeric GTPases because most inflammatory functions of PMN are dependent on dynamic rearrangement of the actin-based cytoskeleton, a process which is well known to be regulated by Rho family GTPases. Their importance in the regulation of PMN functions is further emphasized by the fact that some monomeric GTPases such as Rac1 and Rac2 are part of the multi-component NADPH oxidase and thus play an important role in the regulation of the respiratory burst. Thus, it is of great importance to elucidate the mechanisms by which integrins and pro-inflammatory cytokines regulate monomeric GTPases in human PMN to better understand how inflammatory functions of PMN are regulated during episodes of infection.Recently, I also developed a research project aimed at understanding how e3B1, the human homologue of the Abi1 gene, couples growth factor receptors, such as EGFR, to activation of monomeric GTPases in fibroblasts.