Non-receptor tyrosine kinase
The main function of nRTKs is their involvement in signal transduction in activated T- and B-cells in the immune system.Lyn is activated by stimulation of B-cell receptor, which leads to the recruitment and phosphorylation of Zap70-related nRTK, Syk.Mutations in the Btk gene are responsible for X-linked agammaglobulinemia,[2][3] a disease characterized by the lack of mature B-cells.Unlike receptor tyrosine kinases, nRTKs lack receptor-like features such as an extracellular ligand-binding domain and a transmembrane-spanning region.Upon the binding of ATP and substrate to nRTKs, catalysis of phosphate transfer occurs in a cleft between these two lobes.The SH3 domain is smaller (~60 residues) and binds proline-containing sequences capable of forming a polyproline type II helix.These enzymes can bind to activated signaling complexes at the membrane through PH domain interactions with phosphorylated phosphatidylinositol lipids.[8] Tyrosine kinases of Src family contain the same typical structure: myristoylated terminus, a region of positively charged residues, a short region with low sequence homology, SH3 and SH2 domains, a tyrosine kinase domain, and a short carboxy-terminal tail.[18] In contrast, another mutant of the Jak family Jak2, also lacking the pseudo-kinase domain, was able to mediate growth hormone signaling.This pathologically increased activity of nRTK may be responsible for growth and progression of cancer cells, the induction of drug-resistance, formation of metastasis and tumor neovascularization.Usually monoclonal antibodies are used for the targeted blockade of RTK, which block the extracellular domain of the receptor and prevent the binding of a ligand.