Protein Tyrosine Kinase

Protein tyrosine kinases encompass a large and diverse multi-gene family that regulate cell proliferation, differentiation, metabolism, migration and survival. Both receptor tyrosine kinases and non-receptor tyrosine kinases belong to this family. Receptor tyrosine kinases are a large family of cell surface receptors, containing over fifty members.[1] Receptor tyrosine kinases bind many polypeptide growth factors, cytokines and hormones.[2] Biologically, receptor tyrosine kinases may be divided into several subfamilies such as ErbB,[3] FGFR,[4] VEGFR,[5] RET receptor, Eph receptor,[6] PDGFR,[7] and IGF-1R, and endothelin receptors type A. These receptor families have been found to have a close relationships with humans’ physical and pathological status, therefore, scientific researchers have focused on these signaling pathways in drug discovery and development. Many inhibitors that target one or more receptor, such as lapatinib (ErbB), AZD4547 (FGFR) and BIBF1120 (VEGFR), were created to treat human disease. Non-receptor tyrosine kinases are cytoplasmic enzymes, which are involved in the process of signal transduction in activated T- and B-cells in the immune system. Src, Abl, Syk and Tie2 belong to this family. As an example, many different cellular receptors activate Src family protein tyrosine kinases. The Src family tyrosine kinases participate in signaling pathways that control a diverse spectrum of receptor-induced biological and pharmacological activity. Src inhibitors such as dasatinib and saracatinib were developed to investigate the treatment of cancer.

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[1] Robinson DR, et al. The protein tyrosine kinase family of the human genome. Oncogene. 2000, 19(49): 5548-5557.
[2] Cadena DL, et al. Receptor tyrosine kinases. The FASEB Journal. 1992, 6 (6): 2332-2337.
[3] Kris MG, et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA. 2003, 290(16): 2149-2158.
[4] Eswarakumar VP, et al. Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev. 2005, 16(2): 139-149.
[5] de Vries C, et al. The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science. 1992, 255(5047): 989-991.
[6] Buj-Bello A, et al. Neurturin responsiveness requires a GPI-linked receptor and the Ret receptor tyrosine kinase. Nature. 1997, 387(6634): 721-724.
[7] Wilhelm SM, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004, 64(19): 7099-7109.


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