Signaling pathways tyrosine kinases

This stage involves alteration in gene expression and regulation via cell surface or cytosolic receptors. Most promoters affect gene expression via perturbation of the signal transduction pathways tyrosine kinase, steroid, or G protein linked. The result is cell proliferation. 

The abundance of many protein kinases in cells is an indication of the great importance of protein phosphorylation in cellular regulation. Exactly 113 protein kinase genes have been recognized in yeast, and it is estimated that the human genome encodes more than 1000 different protein kinases. Tyrosine kinases (protein kinases that phosphorylate Tyr residues) occur only in multicellular organisms (yeast has no tyrosine kinases). Tyrosine kinases are components of signaling pathways involved in cell-cell communication (see Chapter 34). 

In general terms, cross talk refers to the interaction between signalling pathways, e.g. between pathways involving heterotrimeric GTP-binding proteins and tyrosine kinase pathways. 

Sorafenib is a multitargeted cancer therapy that inhibits VEGFR, PDGFR, KIT, fetal liver tyrosine kinase 3 (FLT-3), and the serine/threonine kinase RAF. RAF kinase is a key downstream effector of Ras in the MAPK/Ras signal-transduction pathway that has been linked to various cancers. Sorafenib is both a tyrosine kinase inhibitor and serine/threonine signal-transduction inhibitor. Sorafenib has been approved in renal cancer. 

In contrast to tyrosine kinases, Tyrosine phosphatases (PTPs) are enzymes which act on phosphorylated proteins and catalyze the transfer of a phosphate group from a tyrosine residue to a water molecule, generating orthophosphates in a process which is referred to as dephosphorylation. PTPs are involved in many cellular signal transduction pathways. 

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