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Review
. 2022 Nov 30;10(12):3079.
doi: 10.3390/biomedicines10123079.

The Functional Properties and Physiological Roles of Signal-Transducing Adaptor Protein-2 in the Pathogenesis of Inflammatory and Immune Disorders

Jun-Ichi Kashiwakura  1 , Kenji Oritani  2 , Tadashi Matsuda  3
Affiliations
Review

The Functional Properties and Physiological Roles of Signal-Transducing Adaptor Protein-2 in the Pathogenesis of Inflammatory and Immune Disorders

Jun-Ichi Kashiwakura et al. Biomedicines. .

Abstract

Adaptor molecules play a crucial role in signal transduction in immune cells. Several adaptor molecules, such as the linker for the activation of T cells (LAT) and SH2 domain-containing leukocyte protein of 76 kDa (SLP-76), are essential for T cell development and activation following T cell receptor (TCR) aggregation, suggesting that adaptor molecules are good therapeutic targets for T cell-mediated immune disorders, such as autoimmune diseases and allergies. Signal-transducing adaptor protein (STAP)-2 is a member of the STAP family of adaptor proteins. STAP-2 functions as a scaffold for various intracellular proteins, including BRK, signal transducer, and activator of transcription (STAT)3, STAT5, and myeloid differentiation primary response protein (MyD88). In T cells, STAP-2 is involved in stromal cell-derived factor (SDF)-1α-induced migration, integrin-dependent cell adhesion, and Fas-mediated apoptosis. We previously reported the critical function of STAP-2 in TCR-mediated T cell activation and T cell-mediated autoimmune diseases. Here, we review how STAP-2 affects the pathogenesis of T cell-mediated inflammation and immune diseases in order to develop novel STAP-2-targeting therapeutic strategies.

Keywords: T cell antigen receptor (TCR); T cells; immune response; signal transduction; signal-transducing adaptor protein-2 (STAP-2).

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Conflict of interest statement

The authors declare no financial conflict of interest.

Figures

Figure 1
Figure 1
STAP-2 structure and domain-binding proteins. PH, Pleckstrin homology domain; SH2, Src homology 2 (SH2) domain; Pro, Proline-rich region containing a YXXQ motif. The proteins that bind to the domain within STAP-2 are indicated above or below the illustrated STAP-2.
Figure 2
Figure 2
Participation of STAP-2 in LCK-mediated CD3ζ activation. STAP-2 functions as an adaptor protein of LCK and CD3ζ. Once these proteins bind to STAP-2, LCK easily phosphorylates CD3ζ, resulting in the induction of T cell activation events, such as calcium mobilization and IL-2 production.
See this image and copyright information in PMC

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