Isolation and ar terial perfusion of the liver eliminates or significantly

Others have shown that serine phosphoryl ation of cortactin is necessary for N WASP association, The IP experiments performed also revealed that cortactin associates with phospho Erk 1 2 and N WASP upon C. jejuni infection, and that N WASP and phospho Erk 1 2 association with cortactin is dependent INK 128 溶解度 on CiaD, These data show that C. jejuni induces the formation of the actin nucleation and polymerization complex Erk 1 2 cortactin N WASP, and that this associ ation is, in part, dependent of the C. jejuni effector protein CiaD. These data also show that the recruitment of N WASP to cortactin requires Erk 1 2 serine phosphoryl ation of cortactin. Discussion This study was performed to further elucidate the mechan ism of C. jejuni invasion of host cells. More specifically, we investigated the role of Erk 1 2 and cortactin in C.<br>br<> jejuni invasion of host cells. Erk 1 2 is a serine threonine kinase that is part of the Ras Raf MEK ERK signal transduction cascade. Erk 1 2 is activated by dual phosphorylation at Y204 187 and T202 185 catalyzed by MEK 1 2, Erk 1 2 catalyzes the phosphorylation KU-57788 溶解度 of hundreds of cytoplasmic and nuclear proteins and participates in numerous cellular processes including cell adhesion, cell cycle progression, cell migration, cell survival, differen tiation, metabolism, proliferation, and transcription, Cortactin is a filamentous actin binding protein that is a crucial link between the organization of structural proteins, such as actin, and cellular signal transduction pathways.<br>br<> Cortactin stimulates actin polymerization via interaction with N WASP through its SH3 domain, and binding of Arp 2 3 through its N terminal domain, Cortactin is regulated by phosphorylation Linsitinib ic50 of Y421, Y470, and Y486 by c Src and other tyrosine kinases, Likewise, Erk 1 2 phosphorylates S405 and S418 of cortactin, There is also evidence that PAK phosphorylates cortactin, however the implications of PAK serine phosphorylation are poorly defined, Work by Martinez Quiles et al. revealed that phos phorylation of cortactin by Erk 1 2 acts as a positive regu latory event and Src phosphorylation acts as a negative regulatory event in actin cytoskeletal rearrangement by ac tivation deactivation of N WASP and Arp2 3, Add itionally, Kelley et al. demonstrated that concurrent phosphorylation of cortactin by Erk 1 2 and tyrosine ki nases allow cells to regulate actin dynamics through N WASP.<br>br<> Taken together, it is clear that the activation and deactivation of cortactin by phosphorylation is a dynamic process. In the present study, we showed that phosphoryl ation of cortactin on S405, S418, Y421, Y470, and Y486 are required for maximal invasion of host cells by C. jejuni. Specifically, we show that CiaD is required for max imal activation of Erk 1 2, Activation of Erk 1 2 leads to the phosphorylation of S405 and S418 on cortactin, Also, the association of cortactin with Erk 1 2 is dependent on CiaD, Further more, we found that serine phosphorylation of cortactin is required for maximal C. jejuni induced host cell membrane ruffling.