Wiley Interdiscip Rev Syst Biol Med - The adaptor protein LAT serves as an integration node for signaling pathways that drive T cell activation.

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Resumo

T cells are essential for the adaptive immune response to pathogens. However, dysfunctional T cell activity has been implicated in numerous diseases, including the failure of organ transplants, allergic reactions, asthma, autoimmune disorders, and coronary artery disease. T cell responses to pathogens require the induction of the primary activating receptor, the T cell receptor (TCR), along with other costimulatory and adhesion receptors. Signal transduction pathways activated downstream of these receptors drive T cell responses required for the immune response and disease progression. A key question in our understanding of the mechanism of T cell activation is how signaling pathways emanating from multiple receptors integrate together to alter T cell effector functions. One integration node for intracellular signaling is the membrane-associated adaptor protein linker for the activation of T cells or LAT. Upon stimulation of the TCR and other receptors, LAT is phosphorylated at several tyrosines residues on its cytoplasmic tail. This leads to the binding of SH2 domain-containing proteins and their associated molecules and the formation of large multiprotein complexes. These dynamic and highly regulated signaling complexes facilitate the production of second messengers, activate downstream pathways, induce actin cytoskeleton polymerization, and stimulate the activity of multiple transcription factors. Thus, signaling pathways from several receptors feed into LAT, which then integrates this information and selectively induces pathways critical for T cell activation and the adaptive immune response.

Resumo Limpo

t cell essenti adapt immun respons pathogen howev dysfunct t cell activ implic numer diseas includ failur organ transplant allerg reaction asthma autoimmun disord coronari arteri diseas t cell respons pathogen requir induct primari activ receptor t cell receptor tcr along costimulatori adhes receptor signal transduct pathway activ downstream receptor drive t cell respons requir immun respons diseas progress key question understand mechan t cell activ signal pathway eman multipl receptor integr togeth alter t cell effector function one integr node intracellular signal membraneassoci adaptor protein linker activ t cell lat upon stimul tcr receptor lat phosphoryl sever tyrosin residu cytoplasm tail lead bind sh domaincontain protein associ molecul format larg multiprotein complex dynam high regul signal complex facilit product second messeng activ downstream pathway induc actin cytoskeleton polymer stimul activ multipl transcript factor thus signal pathway sever receptor feed lat integr inform select induc pathway critic t cell activ adapt immun respons

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