Role of tyrosine kinases and the tyrosine phosphatase SptP in the interaction of Salmonella with host cells

Salmonella has evolved an intimate functional interface with its host. Cent ral to this interface is a battery of bacterial proteins delivered into hos t cells via a specialized organelle termed the type III secretion system. A subset of these bacterial proteins stimulates cellular responses by activa ting the Rho family GTPases Cdc42 and Rac. Stimulation of these responses l eads to actin cytoskeleton reorganization and the activation of cellular tr anscription factors that result in bacterial uptake and proinflammatory cyt okine production. Remarkably, the cellular responses stimulated by Salmonel la are quickly reversed by another bacterial protein, SptP, which exerts it s function as a GTPase-activating protein (GAP) for Cdc42 and Rac. In addit ion to its GAP activity located within its amino-terminus, the carboxy-term inal domain of SptP possesses potent tyrosine phosphatase activity. We show here that the tyrosine phosphatase activity of SptP is involved in reversi ng the MAP kinase activation that results from Salmonella infection. We als o demonstrate an important role for tyrosine kinases, including ACK, in the cellular responses induced by Salmonella. We also found that a potential t arget for the tyrosine phosphatase activity of SptP is the intermediate fil ament protein vimentin, which is recruited to the membrane ruffles stimulat ed by Salmonella.