A non-receptor tyrosine kinase (nRTK) is cytosolic enzyme that is responsible for catalysing the transfer of a phosphate group from a nucleoside triphosphate donor, such as ATP, to tyrosine residues in proteins. Non-receptor tyrosine kinases are a subgroup of protein family tyrosine kinases, enzymes that can transfer the phosphate group from ATP to a tyrosine residue of a protein (phosphorylation). These enzymes regulate many cellular functions by switching on or switching off other enzymes in a cell.
Unlike the receptor tyrosine kinases (RTKs), the second subgroup of tyrosine kinases, the non-receptor tyrosine kinases are cytosolic enzymes. Thirty-two non-receptor tyrosine kinases have been identified in human cells (EC 22.214.171.124). Non-receptor tyrosine kinases regulate cell growth, proliferation, differentiation, adhesion, migration and apoptosis, and they are critical components in the regulation of the immune system.
The main function of nRTKs is their involvement in signal transduction in activated T- and B-cells in the immune system. Signaling by many receptors is dependent on nRTKs including T-cell receptors (TCR), B-cell receptors (BCR), IL-2 receptors (IL-2R), Ig receptors, erythropoietin (EpoR) and prolactin receptors. CD4 and CD8 receptors on T lymphocytes require for their signaling the Src family member Lck. When antigen binds to T-cell receptor, Lck becomes autophosphorylated and phosphorylates the zeta chain of the T-cell receptor, subsequently another nRTK, Zap70, binds to this T-cell receptor and then participates in downstream signaling events that mediate transcriptional activation of cytokine genes. Another Src family member Lyn is involved in signaling mediated by B-cell receptor. Lyn is activated by stimulation of B-cell receptor, which leads to the recruitment and phosphorylation of Zap70-related nRTK, Syk. Another nRTK, Btk, is also involved in signaling mediated by the B-cell receptor. Mutations in the Btk gene are responsible for X-linked agammaglobulinemia, a disease characterized by the lack of mature B-cells.