Protein tyrosine kinases (PTKs) are a group of enzymes that play crucial roles in cellular communication and regulation. PTKs control key functions of normal and malignant cells. They are ubiquitous enzymes that are integrally involved in the regulation of transformation mechanisms, normal and pathological growth, immune responses, and a variety of intracellular signaling mechanisms. 
PTKs play a fundamental role in various aspects of cell biology, including cell proliferation, survival, adhesion and motility by regulating ligand-mediated signal transduction, cell cycle regulation and progression, cell division, cell differentiation and cytoskeleton functions. Hence, the importance of PTKs in cell growth regulation on multiple levels is evident. Tyrosine kinases have major clinical implications: they activate lymphocytes and mediate communication in cell types like adrenal chromaffin cells, platelets, and neural cells. Dysregulation of PTK-activated pathways, due to mutations, often by receptor overexpression, gene amplification, or genetic mutation, is a causal factor underlying numerous cancers (initiation and progression). Many of the PTKs represent proto-oncogenes and their mutations and/or abnormal expression result in the acquisition of malignant phenotype by the affected cells. In all likelihood, specific types of lymphomas as well as other types of malignancies display distinct patterns of expression of tyrosine kinases (besides other gene families). Identification of such patterns may play an important role in diagnosis of malignant tumors, particularly if the conventional methods yield equivocal results.
PTKs are some of the most frequently altered genes in cancer, either via mutation, overexpression, or amplification. The resultant deregulated cellular signaling contributes to disease progression and drug resistance. Regulation of PTKs is controlled both by extensive post-translational modifications, particularly protein phosphorylation and by changes in PTK abundance. Thus, there is utility in quantifying the expression of PTKs to identify drug response signatures and reveal new biological characteristics.
A tyrosine kinase is an enzyme that transfers a phosphate group from ATP to specific tyrosine residues within proteins. This process acts as an "on" or "off" switch in various cellular functions. PTKs hence mediate the enzymatic transfer of the gamma phosphate of ATP to the phenolic groups on tyrosine residues to generate phosphate monoesters.
- Tyrosine kinases belong to the broader class of protein kinases, which also phosphorylate other amino acids like serine and threonine.
- Phosphorylation by kinases is essential for signal transduction within cells, regulating activities such as cell division.
- These enzymes participate in extracellular signal transmission, affecting gene expression in the nucleus.
- Mutations in tyrosine kinases can lead to uncontrolled cell growth, a hallmark of cancer. Kinase inhibitors are effective cancer treatments.
PTK family of enzymes is generally divided into two groups: receptor PTKs (with more than twelve distinct families) and nonreceptor PTKs (with more than nine distinct families).
Receptor and Non-Receptor Tyrosine Kinases:
- Receptor Tyrosine Kinases (RTKs): These function in transmembrane signaling, receiving signals from outside the cell;
- Non-Receptor Tyrosine Kinases: Operate within the cell, participating in signal transduction to the nucleus.
- Receptor Tyrosine Kinases (RTKs): These function in transmembrane signaling, receiving signals from outside the cell;
- Non-Receptor Tyrosine Kinases: Operate within the cell, participating in signal transduction to the nucleus.
Typically, expression of PTKs is measured by enzyme-linked immunosorbent assay, fluorescence activated cell sorting and immunoblotting, which provide information for a limited number of proteins in a single assay. Multiplexed targeted proteomic assays, on the other hand, could reveal simultaneous alterations of protein expression in entire PTK pathways. A widely used targeted proteomics approach for quantification is multiple reaction monitoring (MRM, also termed selected reaction monitoring), technique that has both advantages and disadvantages.
In summary, protein tyrosine kinases are pivotal players in cellular communication, and understanding their roles helps uncover new therapeutic strategies. Many PTKs have been shown to act as oncogenes and analysis of PTK expression by malignant cells will lead to a better understanding of oncogenesis. This in turn will lead to novel therapies based on selective inhibition of PTKs. The approach has already been proven effective in chronic myeloid leukemia and related bcr/abl-PTK-positive disorders. Expression of PTKs may be determined by RT-PCR using degenerate primers which recognize common, relatively invariable cDNA sequences of members of the PTK family. Other approaches to determine PTKs are also available nowadays, as it was previously mentioned.
PTKs are among the most intensively pursued superfamilies of enzymes as targets for anti-cancer drugs. PTK expression varies between different types and stages of cancer and alterations in PTK expression are an important mechanism of resistance to targeted cancer therapeutics. These considerations suggest that multiplexed, targeted analysis of PTK expression profiles are valuable in studying mechanisms of drug susceptibility and resistance. PTK profiling at the protein expression level may provide a robust alternative to study adaptation of signaling networks in human tumors.
