Signal Pathways Operated by Receptor Protein Tyrosine Kinase

3 Signal pathways operated by receptor protein tyrosine kinase 

There are two main classes of protein tyrosine kinases (PTKs) as cell surface receptors involved in signal transduction. Phosphorylation on Tyr represents an authentic physiological process. While phosphorylation in nontransformed cells occurs mostly on Ser and Thr, phosphorylation in transformed cells includes Ser, Thr and Tyr residues. Thus Tyr phosphorylation is intimately linked to cell proliferation/transformation. Tyrosine phosphorylation is not limited to the actions of the transforming viruses or growth factors. It regulates a number of important signaling processes including  

The activated receptors for EGE and PDGF stimulate PLCy. This results in the generation of DAG and IP3, leading to the activation of PKC and a rise in the concentration 

Another type of domain that recognizes phosphotyrosine residues is the PTB (phosphotyrosine binding) domain (alternatively, phosphotyrosine interaction domain, PID). The specificity of interaction is determined by the sequence of amino acids immediately on the N-terminal side of the phosphorylated tyrosine, NPXYp. The tertiary structure shows a p-barrel structure and a long a-heUx that packs against one end. The target phosphotyrosine binds to one side of the P-barrel. 

The mitogenic signal initiated by growth factors requires an increased rate of protein synthesis and probably also the selective translation of specific mRNAs. ERK initiates ribosomal protein synthesis by regulating the binding of the initiation factor-4E (eIF-4E) to the cap of the mRNA and to the initiation factor complex. Activation of ERK results in phosphorylation of eIF-4E at Ser-209 via MNKl and eIF-4G. Association of eIF-4E with other components of initiation complex has the effect of ironing out a hairpin loop close 

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