Cell adhesion to the extracellular matrix substratum affects multiple cellular responses that include gene expression, differentiatio, cell viability and morphology. Our long term goal is to identify the intracellular signals transduce,. and the pathways that are activated, when cells adhere and spread on surfaces.
Integrins are a family of dimeric transmembrane receptors that mediate cell binding to extracellular matrix proteins. Platelets are used in our studies to investigate the mechanism by which integrins regulate cell spreading. These studies are important since the arrest of bleeding is dependent on the ability of platelets to aggregate and spread. We have previously shown that platelet adhesion and spreading on fibrinogen correlates with the induction of tyrosine phosphorylation of several proteins. We identified one of these proteins as the ubiquitously expressed cytoskeletal protein, alpha-actinin. We have also found that alpha-actinin is phosphorylated by the focal adhesion kinase, pp125FAK. One of our current interests is to identify the phosphatase that regulates the state of phosphorylation of alpha-actinin. Research effort is also focused on elucidating the role of tyrosine phosphorylation of the actin binding protein vinculin.
A second line of investigation in our laboratory is currently focused on theenteric pathogen Shigella which causes dysentery in humans. While rare in Western countries, the number of deaths attributed to Shigella in third world countriesexceeds one million per year. The majority of the casualties (>65%) are children under the age of five. Virulent Shigella species trigger a strong inflammatory reaction. Our goal is to develop an understanding of the mechanism by which Shigella targets and affects human inflammatory cells.