Lymphocyte-specific protein tyrosine kinase (Lck) and Fyn proto-oncogene (Fyn) (Lck/Fyn)

Lck (Lymphocyte-specific protein tyrosine kinase) and Fyn (Fyn proto-oncogene) are non-receptor tyrosine kinases belonging to the Src family, primarily expressed in T cells and natural killer (NK) cells [1.1.3, 1.5.3]. They are essential for the initiation of T-cell receptor (TCR) signaling, where they phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs) on the CD3 and zeta chains upon antigen recognition [1.3.1, 1.3.2]. Lck is generally considered the primary initiator of proximal signaling and is critical for thymocyte development, while Fyn plays a complementary role in signal amplification and the regulation of specific immune responses, such as NK T cell development [1.3.4, 1.3.5]. Dysregulation, overexpression, or hyperactivation of Lck and Fyn are associated with various diseases, including T-cell acute lymphoblastic leukemia (T-ALL), chronic lymphocytic leukemia (CLL), and autoimmune disorders like rheumatoid arthritis [1.2.1, 1.5.1, 1.5.2]. Therapeutic targeting of these kinases, often simultaneously using multi-kinase inhibitors like dasatinib, has shown efficacy in suppressing leukemic cell growth and modulating immune responses [1.1.2, 1.2.2]. However, inhibition of these targets carries risks of significant immunosuppression and off-target toxicities due to their high homology with other Src family members [1.4.1].

Other names

p56lckp59fynLSKYT16IMD22SLKSYNpp58lckSrc family tyrosine kinase LckSrc family tyrosine kinase Fyn

Tyrosine kinase inhibition