NRTK Pathway
Phosphate groups are added to tyrosine residues on protein substrates by enzymes known as protein tyrosine kinases (PTKs). Proteins can alter in function and/or enzymatic activity by phosphorylation, and these changes trigger particular biological reactions. PTKs are divided into two classes: cytoplasmic non-receptor PTKs and transmembrane receptor PTKs (NRTKs). NRTKs participate in the transmission of extracellular signals, which frequently interact with transmembrane receptors. As a result, they play a crucial role in signaling pathways that control essential biological processes such as cell differentiation, death, survival, and proliferation. The activity of NRTKs is closely controlled, and overexpression or deregulation of NRTKs has been linked to cancer development and malignant transformation.
The mechanics of numerous cellular processes, including those implicated in carcinogenesis, have been clarified through research on NRTKs. It should come as no surprise that a number of tyrosine kinase inhibitors are currently being used to treat a variety of cancers, and others are being researched. The nine major families of NRTKs and their signaling pathways in both healthy and malignant cells are the topics of this review.
Non-Receptor Tyrosine Kinase Signaling
Non-receptor tyrosine kinases (NRTKs), which can activate intracellular signals generated from external receptors, are a subset of tyrosine kinases, intracellular cytoplasmic proteins, or tethered to the cell membrane. Based mostly on similarities in the kinase domain sequences, they can be divided into nine subfamilies. These are the kinases from the ABL, FES, JAK, ACK, SYK, TEC, FAK, SRC, and CSK families.
NRTKs, which have a great deal of structural variety, don’t have receptor-like characteristics such as an extracellular ligand-binding domain or a transmembrane-spanning domain. They are made up of a large cytoplasmic C-terminal region and an N-terminal section of a common kinase domain that spans around 300 residues. Additionally, they frequently contain a number of extra SH2, SH3, and PH domains, which are signaling or protein-protein interaction domains. The protein substrate’s tyrosine sequence interacts with the residues of the C terminal domain by the binding of the ATP molecule between the two domains.