Background Information:

Tyrosine phosphorylation represents a major mechanism for the activation of signal transduction pathways in response to growth factors, hormones and cytokines. There are approximately 100 tyrosine kinases that are both receptor tyrsosine kinase receptors for various growth factors and cytokines. The extent and duration of tyrosine phosphorylation are tightly regulated by the 107 protein tyrosine phosphatases. Tyrosine phosphorylation occurs on residues on either other kinases (Ser/Thr or Tyr) or on substrates. In the case of kinases, this phosphorylation often causes the enzyme to change activation states and/or it creates binding sites for SH2 domain. Mutation or misregulation of protein tyrosine kinases is a cause or consequence of many disease states. It has been estimated that 20% of oncogenes so far described are tyrosine kinases. With such clear links between aberrant protein tyrosine kinase activity and disease, it is no surprise that much of the early effort in kinase drug discovery was focused on these enzymes.