Mechanism of Tyrosine Kinase
Reference: Graphics and activity descriptions taken from Cell Biology Home Page of  Donald Slish, Plattsburg State University, Dept of Cell Biology

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1. Tyrosine kinase receptors are a family of receptors with a similar structure. They each have a tyrosine kinse domain (which phosphorylates proteins on tyrosine residues), a hormone binding domain, and a carboxyl terminal segment with multiple tyrosines for autophosphorylation.
When hormone binds to the extracellular domain the receptors aggregate.



2. When the receptors aggregate, the tyrosine kinase domains phosphorylate the C terminal tyrosine residues.



3. This phosphorylation produces binding sites for proteins with SH2 domains. GRB2 is one of these proteins. GRB2, with SOS bound to it, then binds to the receptor complex. This causes the activation of SOS.



4. SOS is a guanyl nucleotide-release protein (GNRP). When this is activated, it causes certain G proteins to release GDP and exchange it for GTP. Ras is one of these proteins. When ras has GTP bound to it, it becomes active.



5. Activated ras then causes the activation of a cellular kinase called raf-1.


6. Raf-1 kinase then phosphorylates another cellular kinase called MEK. This cause the activation of MEK.



7. Activated MEK then phosphorylates another protein kinase called MAPK causing its activation. This series of phosphylating activations is called a kinase cascade. It results in amplification of the signal.



8. Among the final targets of the kinase cascade are transcriptions factors (fos and jun showed here). Phosphorylation of these proteins causes them to become active and bind to the DNA, causing changes in gene transcription.