Regions outside of conserved PxxPxR motifs drive the high affinity interaction of GRB2 with SH3 domain ligands.

SH3 domains are evolutionarily conserved protein interaction domains that control nearly all cellular processes in eukaryotes. The current model is that most SH3 domains bind discreet PxxPxR motifs with weak affinity and relatively low selectivity. However, the interactions of full-length SH3 domain-containing proteins with ligands are highly specific and have much stronger affinity.

The adaptor protein LAT serves as an integration node for signaling pathways that drive T cell activation.

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.

T cell receptor activation leads to two distinct phases of Pyk2 activation and actin cytoskeletal rearrangement in human T cells.

The tyrosine kinase Pyk2 integrates receptor-mediated signals controlling actin cytoskeletal rearrangement, events needed for the activation and function of T cells. Induction of the T cell receptor (TCR) leads to the phosphorylation of Pyk2, but the timing of these events is controversial and not fully understood. In this study, the TCR-induced phosphorylation kinetics of Pyk2 tyrosines 402 and 580 were characterized in human T cells.

Comparison of T cell receptor-induced proximal signaling and downstream functions in immortalized and primary T cells.

Background: Human T cells play an important role in pathogen clearance, but their aberrant activation is also linked to numerous diseases. T cells are activated by the concurrent induction of the T cell receptor (TCR) and one or more costimulatory receptors. The characterization of signaling pathways induced by TCR and/or costimulatory receptor activation is critical, since these pathways are excellent targets for novel therapies for human disease.