LYN (LYN Proto-Oncogene Src Family Tyrosine Kinase)

Mechanistically, Tus inhibited tolimidone-induced Lyn kinase activation and suppressed SP-and Tween 80-induced β-hexosaminidase release, exhibiting an inhibitory profile comparable to that of the Lyn/Btk antagonist bosutinib. Additionally, Tus attenuated the phosphorylation levels of MRGPRX2 downstream signal molecules, including Btk, PLCγ1, PKC, p38 MAPK, IκB-α and NF-κB (p65). In conclusion, Tus attenuates SP-and Tween 80-induced mast cell activation and pseudo-allergic reactions by targeting the Lyn/Btk/PLCγ1 and p38/NF-κB pathways, highlighting its therapeutic potential for pseudo-allergy.

Collectively, the PDZK1-ULK1 axis regulates LD homeostasis in ccRCC. Targeting this axis via ULK1 activation represents a novel strategy to overcome sunitinib resistance, with ULK1 as a potential biomarker for sunitinib efficacy.

These cells exhibited persistently impaired cytotoxic programs (e.g., GNLY), a de-differentiated memory-like state, elevated PDCD1 expression, and reduced TCR diversity. Together, this study provides the first single-cell framework of tumor clonal evolution and T-cell dysfunction under ibrutinib in WM; introduces the WIP score as a predictive biomarker for treatment response; and identifies actionable tumor-intrinsic and immune mechanisms driving resistance.

These findings indicate a causal relationship between the pathological process of neurogenic heterotopic ossification following spinal cord injury and the activation of the CXCL12-CXCR4-phosphatidylinositol 3-kinase-protein kinase B signaling axis, which modulates bone marrow mesenchymal stem cell function through M1 macrophage polarization. This study reveals a key mechanism driving the osteogenic differentiation of bone marrow mesenchymal stem cells, providing new directions for early warning and targeted treatment of neurogenic heterotopic ossification following spinal cord injury.

MIR31 deletion upregulates LYN, enhancing stiffness perception and tipping the balance toward O-GlcNAc addition to NICD1, finally resulting in mechanoadaptation- and tumor stemness-driven recurrence. Consequently, MIR31 deletion is a potential biomarker for recurrence and patient stratification in Notch- or OGT-targeted therapies.

Beyond oncology, emerging evidence links Lyn kinase to neuroinflammation, synaptic dysfunction, and metabolic regulation, further underscoring its broad disease relevance. Lyn kinase is considered a viable therapeutic target, with ongoing research focusing on small-molecule inhibitors, monoclonal antibodies, and natural compounds like flavonoids and polyphenols that have exhibited promising preclinical and clinical outcomes. We summarized current insights into Lyn kinase biology, highlighting its pathological significance and discussing therapeutic opportunities arising from the modulation of this enzyme.

Thus, we define a novel N-degron pathway that monitors replacement of myristoylation by acetylation and activates degradation of SFKs upon acetylation. This mechanism may extend to other N-terminally myristoylated proteins beyond SFKs.

Across pooled cohorts, LYN mutation is associated with increased odds of CNS metastasis, and domain context appears informative, with a small-sample, FDR-borderline enrichment at the SH4/Unique N-terminus. The truncating-class signal is exploratory given limited power. Signals by domain (notably SH4/Unique) are exploratory and require independent validation in larger, uniformly annotated datasets. Given small mutant denominators and ever-CNS endpoint capture, findings are hypothesis-generating and not actionable for risk stratification or treatment selection. Results motivate domain-aware annotation in future validation studies and mechanistic work.

Our results also indicate an association between CCT/TRiC chaperonins and the regulation of tubulin/actin, supporting their involvement in cytoskeleton dynamics, the mitotic spindle, chromosome segregation, and autophagy/aggrephagy. Overall, our findings expand the repertoire of chaperone client proteins and provide insights into how chaperone dysregulation influence breast cancer biology, highlighting their potential as therapeutic targets.

In vivo, TSN ameliorated dextran sulfate sodium (DSS)-induced colitis in mice while downregulating STING pathway components. These findings demonstrated that TSN achieved its anti-inflammatory effects by suppressing the STING pathway through direct binding to both LYN and STING proteins, suggesting its therapeutic potential for UC and other conditions involving aberrant STING activation.

Immunohistochemically, SHP-1 levels were negatively correlated with pLyn/Lyn levels in DLBCL tissues. Overall, these results suggest that SET antagonism to inactivate Lyn represents an attractive approach for DLBCL treatment.

Additionally, LynAKO and LynBKO macrophages were as hyperproliferative as LynKO cells. These data suggest that Lyn promotes macrophage activation in response to TLR signaling and restrains aberrant proliferation and matrix deposition in a dose-dependent rather than isoform-specific manner.