Abstract
T cells play a pivotal role in adoptive immunity, both in cell mediated cytotoxicity and in the activation of the humoral immune response. In order to perform their effector function, T cells undergo dramatic morphological changes upon activation. These changes enable their binding to and extravasation through the vascular endothelium into the neighboring tissue, the formation of an immunological synapse (IS) with an antigen-presenting cell (APC), and subsequently, the polarized secretion of cytokines and/or cytolytic granules, leading to the execution of effector functions. The actin cytoskeleton is directly involved in all these processes. Thus, it is crucial for T cell mediated immune responses, providing a dynamic and flexible platform for signal transduction, cellular and subcellular remodeling, and for driving effector functions. The actin-regulatory proteins, Wiskott-Aldrich syndrome protein (WASp) and WASp family Verprolin-homologous protein (WAVE) play key roles in T cell biology. In this review, we will focus on these two proteins, describing their structure, recruitment, activation and function. Finally, we will address pathological aspects related to defects in these actin regulators.
Highlights
Protein phosphorylation is a ubiquitous posttranslational process mediated by kinases and serves to regulate the activation state of numerous proteins
The current dogma, that PKCθ regulates nuclear factor-κB (NF-κB) activity through its effect on IKK-IκBα, is further substantiated by in vivo studies demonstrating that T cells from PKCθ-deficient (Prkcq-/-) mice fail to respond to TCR stimulation with degradation of IκBα [45]
Past studies have established the requirement for PKCθ in the regulation of many fundamental processes in T cell biology (Figure 2)
Summary
Protein phosphorylation is a ubiquitous posttranslational process mediated by kinases and serves to regulate the activation state of numerous proteins. Immunological studies using different genetic models and pharmacological drugs indicated that distinct PKC isoforms are required for different aspects of the activation and effector function of T cells.
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