Intra-cellular tyrosine kinase

Introduction Protein kinases are proteins that enzymatically add a phosphate, obtained from ATP, to an OH group on certain amino acids in a protein. They are divided into two major groups: serine/threonine kinases phosphorylate serine or threonine residues; tyrosine kinases phosphorylate tyrosine residues (1). Dual-specificity kinases, such as Mek, phosphorylate all three amino acid residues. Phosphorylation causes a conformational change in the target protein by the addition of a bulky, charged group (Figure 19.1) to the protein. This causes alteration of the activity, subcellular location, or protein–protein interactions of phosphorylated proteins. Phosphorylation is a rapid method of activating and inactivating proteins and significantly altering pathway activities. Phosphorylation regulates cell adhesion, cell-cycle progression, transcription-factor activity, and general metabolism in the cell. As a result, phosphorylation events must be tightly regulated. Most tyrosine kinase targets have an associated protein phosphatase, designed to reverse the effects of phosphorylation rapidly. Often phosphorylation results in the addition or removal of a regulatory protein that either interferes with binding of the target protein to a substrate or maintains it in a separate subcellular compartment away from the substrate. Perturbation of the pathways can cause dysregulation of cellular activities and lead to a number of disorders, including malignancy. It has been stated that cancer is fundamentally a disease of aberrant kinase activity and signal transduction (2).