Occurs as a result of a disturbed Gardens signaling, where mutations can affect certain oncogenic signaling pathways h More often than others. The extracellular Signals are re verst RKT and transduced into cells by cascades of protein kinases, is activated by receptor tyrosine phosphorylation or by coupling to receptor proteins GTPbinding. Protein kinases k May be important regulators Bergenin Cuscutin of intracellular Ren signal transduction, the T ACTION normally be tightly regulated. However, mutant alleles of protein kinases of these genes, or other oncogenes that signal through the cascade of protein kinases, leading to St Requirements of the entire signaling networks, the deregulation of the two transient VORG Length, such as Ver Changes in the cell morphology or motility t or less reversible processes such as cell differentiation, division and apoptosis.
1.1. Protein kinases as targets for anti-cancer agent in the search for small molecule therapeutics for the treatment of cancer have, protein kinases are attractive targets. The complexity t and the number of protein kinases has been used as molecular targets in drug discovery has increased dramatically. The cost of the sequential lacing the Human Genome Project revealed that 600 protein kinases and phosphatases 130 proteins Are probably in the human genome to pr Sentieren. Divided based on their catalytic specificity of t, both classes of enzymes l sst into three categories: those special tires that are specific for serine / threonine, and those specific for both Tyr and Ser / Thr.
Therefore, in the first N Approximation, each cell has a staff of 50 100 protein kinases, which will inevitably reach targeted the question of whether selectivity T and specificity of t k not Can by competitive protein kinase inhibitors ATP-binding site . Recent advances in molecular pathogenesis of cancer have shown that many protein kinases upstream / downstream of epidemiologically relevant oncogenes or tumor suppressors can be found. In particular, the kinase receptor protein tyrosine attracted much attention because their PTK activity is t ligandinducible in untransformed cells usually tightly regulated, but if it mutates or comparable Can be changed structurally transforming. In fact, more than 50% of known rPTK were found repeatedly, with b Sartigen tumors. Retroviral transduction of protein kinases is a fundamental un Change mechanisms in rodents and chickens.
However, the involvement of protein kinases in the development and maintenance of malignant tumors in humans may result from: genomic rearrangements, including normal chromosomal translocations that fusion proteins to generate the catalytic domain ne and an unbound protein is normally the activation function, for example Bcr Abl myeloid leukemia chemistry of chronic, mutations that constitutively activated kinase activity of t, with multiple tumors, Including myeloid leukemia associated lich chemistry acute and gastrointestinal tumors, but a few, deregulation of the kinase activity of t by the activation of oncogenes or loss of tumor suppressor function, which appears to call for example, deregulated in cancer with oncogenic Ras and Raf kinase activity t, or deregulation of the kinase activity of t cyclindependent radio by the loss of tumor suppressor genes