Sentinel node is the first point of contact be tween tumor associated antigens

These findings provide the basis for a detailed model of C. jejuni invasion INK 128 ic50 of host cells, Previous work has shown that Dock180 and its bind ing partner ELMO form a bipartite guanine nucleotide exchange factor, resulting in the activation of Rac1 and membrane ruf fling, C. jejuni invasion of cells is also accompanied by the activation of Cdc42, Interestingly, several effector proteins from Salmonella enterica, including SopE, SopE2 and SopB, modulate the activity of Cdc42 and Rac1 to manipulate actin cytoskeleton rearrange ments, Noteworthy is that the IcsA effector protein from Shigella flexneri promotes filopodia forma tion by binding and activating N WASP in a Cdc42 like fashion, To determine the role of CiaD in C.<br>br<> jejuni in vasion of host cells, we first evaluated the Rho GTPases Rac1 and Cdc42 as a loss in the activation of either protein could explain the invasion deficiency of the ciaD mutant. INT 407 cells infected with the C. jejuni ciaD mutant exhibited levels of Rho GTPase activation similar to that of cells infected KU-57788 ic50 with the C. jejuni wild type strain. This is in stark contrast to cells infected with a C. jejuni ciaC mutant that display a significant reduction in Rac1 activation, The reduction in Rac1 activity with the C. jejuni ciaC mutant is in agreement with the fact that there are fewer sites of co localized Rac1 in INT 407 cells infected with the C. jejuni ciaC mutant versus a C. jejuni wild type strain, Our data supports the pro posal that CiaD is manipulating cellular signaling cascades and altering actin nucleation at a site downstream from Rac1 and Cdc42.<br>br<> Moreover, buy Lonafarnib our results indicate that CiaC and CiaD manipulate at least two distinct host cell targets that are necessary for C. jejuni invasion of host cells. Based on the observation that Erk 1 2 is critical for C. jejuni invasion of host cells, we performed experiments to determine if: 1 Erk 1 2 is transcriptionally regulating cellular components involved in cell invasion; and or 2 Erk 1 2 is necessary for the activation of cytosolic cellular signaling cascades involved in cytoskeleton rearrangement. We found that the transcription of the gene that encodes for IL 8 is not required for invasion, but that Erk 1 2 is re quired for the serine phosphorylation of cortactin.<br>br<> As pre viously stated, cortactin is an actin binding protein that recruits N WASP and activates Arp 2 3, leading to actin remodeling, Interestingly, Erk 1 2 activation stimu lates bacterial capture of Shigella by filopodia, while the OspF effector protein from Shigella harbors phosphat ase activity to inactivate mitogen activated protein kinases, including Erk 1 2, c Jun N terminal kinase, and p38, post invasion, Collectively, these data highlight the fact that Erk 1 2 is a key component of the C. jejuni invasion complex and that bacterial pathogens can ma nipulate membrane extensions by targeting Erk 1 2. Cortactin is likely involved in the uptake of patho genic bacteria into host cells, as it acts in concert with N WASP to activate the Arp2 3 complex. It is plausible for a pathogen to activate cortactin directly or to acti vate cortactin indirectly via Erk 1 2 or Src.