STAP2, also known as signal-transducing adaptor protein 2, is an adaptor molecule involved in regulating multiple intracellular signaling pathways. It contains a pleckstrin homology domain at the N-terminus, an src homology domain in the central portion and a proline-rich region at the C-terminus, and has a YXXQ motif which can bind to STAT3. It influences STAT3 and STAT5 activity, integrin-mediated T cell adhesion, chemokine-induced T cell migration, Fas-mediated T cell apoptosis, Toll-like receptor-mediated macrophage functions, macrophage colony-stimulating factor-induced macrophage activation, and high-affinity immunoglobulin E receptor-mediated mast cell activation. Genetic models are valuable for studying its function in various biological processes and diseases [2,3].

In renal fibrosis, in vivo gene knockout of STAP2 in mice significantly mitigated epithelial-mesenchymal transition, diminished inflammatory cell infiltration, and reduced collagen deposition. Conversely, in vitro assays with STAP2-overexpressing cell models exacerbated the expression levels of fibrosis markers. This indicates that STAP2 promotes the progression of renal fibrosis possibly through modulating phosphorylated HSP27 expression and the PI3K/AKT signaling pathway [1].

In summary, STAP2 is crucial in regulating immune and inflammatory responses as well as cell-related functions. The gene knockout mouse models have revealed its role in renal fibrosis, suggesting that targeting STAP2 could potentially be a strategy for treating renal fibrosis.

References:

1. Yuan, Yuan, Wei, Xiao, Xiong, Xi, Li, Lili, Luo, Pengcheng. 2024. STAP2 promotes the progression of renal fibrosis via HSP27. In Journal of translational medicine, 22, 1018. doi:10.1186/s12967-024-05776-6. https://pubmed.ncbi.nlm.nih.gov/39533293/

2. Ichii, Michiko, Oritani, Kenji, Toda, Jun, Matsuda, Tadashi, Kanakura, Yuzuru. 2021. Signal-transducing adaptor protein-1 and protein-2 in hematopoiesis and diseases. In Experimental hematology, 105, 10-17. doi:10.1016/j.exphem.2021.11.002. https://pubmed.ncbi.nlm.nih.gov/34780812/

3. Matsuda, Tadashi, Oritani, Kenji. . STAP-2 Adaptor Protein Regulates Multiple Steps of Immune and Inflammatory Responses. In Biological & pharmaceutical bulletin, 44, 895-901. doi:10.1248/bpb.b21-00224. https://pubmed.ncbi.nlm.nih.gov/34193686/