<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "The S-acylation switch in activated T cells"^^ . "S-acylation is a reversible post-translational modification involving the covalent attachment of a fatty acid to a cysteine residue of a protein. This modification can influence\r\nprotein conformation, localization, and protein-protein interactions. Due to its reversibility, S-acylation functions as a regulatory switch in various cellular processes, including\r\nT cell activation.\r\nMorrison et al. explored the S-acylome of resting and activated T cells using mass\r\nspectrometry and identified 88 proteins exhibiting changes in their state of S-acylation\r\nupon T cell stimulation. This thesis further investigates three of these proteins and their\r\npossible role in the regulation of T cell signaling by reversible S-acylation:\r\n1. Cytoskeleton associated protein 4 (CKAP4) is dynamically deacylated at cysteine100 upon Dickkopf1 (DKK1) binding in pancreatic cancer cells and is associated with key\r\nprocesses of T cell signaling such as calcium mobilization and cell migration. However,\r\nits role in T cell activation has not been explored before. In this study, the deacylation\r\nswitch of CKAP4 could be confirmed and fundamental groundwork was laid to study\r\nthe localization of CKAP4 in T cells by demonstrating that CKAP4 is only present in\r\nsmall amounts at the T cell plasma membrane. Moreover, CKAP4-3xALFA-Halo cells\r\nwere generated enabling live-tracking of the protein following T cell activation.\r\n2. Family with sequence similarity 49 member B (FAM49B) plays a role in cytoskeletal remodeling and Erk phosphorylation taking place during T cell signaling. Although\r\nS-acylation of FAM49B has been observed before, its exact site and functional relevance\r\nremain unclear. Here, S-acylation of FAM49B could be corroborated and preliminary\r\ndata suggested that cysteine-10 is a potential S-acylation site.\r\n3. Retinitis pigmentosa 2 activator of ARL3 GTPase (RP2) is implicated to play a\r\nrole in the transport of lymphocyte-specific protein tyrosine kinase (Lck), a key enzyme\r\nin T cell signaling. While S-acylation of RP2 at cysteine-3 is documented, its functional\r\nrole is not fully understood and there is no established link between S-acylation of RP2\r\nand T cell activation. For RP2 it was found, that overexpression in T cells induced\r\nincreased levels of Erk phosphorylation in a S-acylation-dependent manner, pointing\r\ntowards its involvement in T cell activation.\r\nMoreover, CKAP4, FAM49B and RP2 knock-outs in T cells were generated and tools\r\nto study their role in T cell activation were established.\r\nIn summary, this thesis provides new insights into the regulatory role of S-acylation\r\nin T cell activation, sets the stage for further studies of S-acylation-switches of proteins\r\nby establishing important experimental tools, and highlights avenues for future research\r\nof this reversible modification in immune signaling."^^ . "2026" . . . . . . . "Helena"^^ . "Brandt"^^ . "Helena Brandt"^^ . . . . . . "The S-acylation switch in activated T cells (PDF)"^^ . . . "The S-acylation switch in activated T cells (Other)"^^ . . . . . . "The S-acylation switch in activated T cells (Other)"^^ . . . . . . "The S-acylation switch in activated T cells (Other)"^^ . . . . . . "The S-acylation switch in activated T cells (Other)"^^ . . . . . . "The S-acylation switch in activated T cells (Other)"^^ . . . . . "HTML Summary of #36179 \n\nThe S-acylation switch in activated T cells\n\n" . "text/html" . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .