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Tyrosine Kinase

Protein-tyrosine kinases (PTKs) catalyze the transfer of the γ-phosphate of ATP to tyrosine residues of protein substrates, are critical components of signaling pathways that control cellular proliferation and differentiation. Two classes of PTKs are present in cells: the transmembrane receptor PTKs and the nonreceptor PTKs.Humans express at least 90 tyrosine kinases, including 58 receptor tyrosine kinases (RTKs). RTKs are activated through binding of their extracellular domain to ligands, such as growth factors and cytokines. This ligand binding results in RTK dimerization/oligomerization and subsequent tyrosine phosphorylation. Over 50% of the 90 tyrosine kinases identified have been implicated in cancer despite the fact that tyrosine phosphorylation represents only 1% of the total phosphoproteome. The disproportionate contribution of tyrosine kinases to cancer further highlights the need to understand the signaling networks initiated by tyrosine kinases as well as how to effectively target them.
Tyrosine kinases are primarily classified as receptor tyrosine kinase (RTK) e.g. EGFR, PDGFR, FGFR and the IR and non-receptor tyrosine kinase (NRTK) e.g. SRC, ABL, FAK and Janus kinase.Structural studies of the catalytic core of several RTKs, supported by biochemical and kinetic studies of receptor phosphorylation have provided proof that receptor oligomerization increases the local concentration of the RTKs, leading to efficient transphosphorylation of tyrosine residues in the activation loop of the catalytic domain. Upon tyrosine phosphorylation the activation loop adopts an open conformation that gives access to ATP and substrates and makes ATP transfer from Mg-ATP to tyrosine residue on the receptor itself and on cellular proteins involved in signal transduction.

References:

1.Justin M. Drake et al.Mol Cell Biol. 2014 May; 34(10): 1722–1732.  
2.Manash K. Paul and Anup K. Mukhopadhyay. Int J Med Sci. 2004; 1(2): 101–115.