Tyrosine-protein kinase Lyn (LYN) (LYN)

Tyrosine-protein kinase Lyn is a non-receptor tyrosine kinase belonging to the Src family (SFK), primarily expressed in hematopoietic cells, neural tissues, and adipose tissue [1, 4]. It plays a dual role in cellular signaling, acting as a "rheostat" that can both positively and negatively regulate pathways such as B-cell receptor (BCR) signaling through the phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAM) and inhibitory motifs (ITIM) [4, 7, 9]. Beyond its critical role in immune cell activation and tolerance, Lyn is involved in erythropoiesis, mast cell degranulation, and insulin signaling [5, 8, 9]. Dysregulation of Lyn activity is implicated in various pathologies, including hematological malignancies like acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), as well as solid tumors such as prostate and breast cancer [1, 6, 11]. It also plays a significant role in autoimmune disorders like systemic lupus erythematosus (SLE) and neurodegenerative conditions like chorea-acanthocytosis [11, 12]. Therapeutic targeting of Lyn typically involves small-molecule inhibitors that competitively bind to its ATP-binding site, with drugs like dasatinib and nilotinib showing activity against it [3, 11, 12]. However, its complex dual regulatory nature presents challenges in drug development, as inhibition may lead to unintended immune dysregulation or off-target toxicities [1, 7, 14].

Other names

LYNJTK8p53Lynp56LynLck/Yes-related novel protein tyrosine kinaseV-yes-1 Yamaguchi sarcoma viral related oncogene homologLYN proto-oncogene, Src family tyrosine kinaseSAIDV

ATP-competitive inhibition of the kinase domain, preventing phosphorylation of tyrosine residues on substrate proteins and modulating ITAM/ITIM-mediated signaling pathways [3, 11].