Tyrosine-phosphorylation-dependent translocation of the SLAT protein to the immunological synapse is required for NFAT transcription factor activation.

SWAP-70-like adaptor of T cells (SLAT) is a guanine nucleotide exchange factor for Rho GTPases that regulates the development of T helper 1 (Th1) and Th2 cell inflammatory responses by controlling the Ca(2+)-NFAT signaling pathway. However, the mechanism used by SLAT to regulate these events is unknown. Here, we report that the T cell receptor (TCR)-induced translocation of SLAT to the immunological synapse required Lck-mediated phosphorylation of two tyrosine residues located in an immunoreceptor tyrosine-based activation motif-like sequence but was independent of the SLAT PH domain.

T regulatory cells in autoimmune diabetes: past challenges, future prospects.

Introduction: Accumulating evidence suggests that defective regulation is an essential underlying cause of autoimmunity. The development of type 1 diabetes in the NOD mouse strain it is a complex process that depends on a fine balance between pathogenic and regulatory pathways.

Discussion: We have utilized a series of transgenic and knockout mice to determine the relative importance of regulatory T cells and negative regulatory receptors on the development and progression of type 1 diabetes.

Cutting edge: CD28-mediated transcriptional and posttranscriptional regulation of IL-2 expression are controlled through different signaling pathways.

Despite the clear functional importance of CD28 costimulation, the signaling pathways transduced through CD28 have remained controversial. PI3K was identified early as a candidate for CD28 signaling, but conflicting data during the past decade has left the role of PI3K unresolved. In this report, we have resolved this controversy.

Role for protein kinase Ctheta (PKCtheta) in TCR/CD28-mediated signaling through the canonical but not the non-canonical pathway for NF-kappaB activation.

NF-kappaB is a family of essential transcription factors involved in both embryonic development and inflammatory responses of the immune system. NF-kappaB can be activated by two pathways, i.e.

Perspectives on PKCtheta in T cell activation.

Upon stimulation by environmental signals, T lymphocytes develop an intricate set of signal-dependent responses including remodeling of the actin cytoskeleton, the development of cellular polarity, the initiation of second-messenger cascades, entry into cell cycle, differentiation and effector function. The integration of TCR and costimulatory signaling is critical to the successful initiation of the T cell activation program, and the serine/threonine kinase PKCtheta is an important site of signal integration in the process of T cell activation. We provide an overview of T cell signaling, and then go on to assess our understanding of the regulation of PKCtheta activity, its target proteins and its role in T cell activation and the production of T cell survival factors such as IL-2.

Ordered just so: lipid rafts and lymphocyte function.

Immunologists have long been occupied with the description of cellular activation signaling events that originate with the stimulation of multichain immunoreceptors at the cell surface. These signals are transmitted by a protein-partner-signaling cascade through the cytoplasm to the nucleus, where they culminate in changes in gene expression, metabolic state, and entry into cell cycle. For T cells and B cells, these signaling cascades start with the ligation of the T cell receptor (TCR) and B cell receptor (BCR), respectively, and result in the recruitment and activation of related families of signaling molecules at the cell surface.