病理學(xué)與病理生理學(xué)總論：GPCR,RTK

1、GPCR,Regulation of G-Protein Activity,Regulation of G-Protein Activity,RTK,Mechanism of Tyrosine Kinase Receptors,When hormone binds to the extracellular domain the receptors aggregate,When the receptors aggregate, the tyrosine kinase domains phosphorylate the C terminal tyrosine residues,Mechanism

2、of Tyrosine Kinase Receptors,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.,Mechanism of Tyrosine Kinase Receptors,SOS is a guanyl nucleotide-

3、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.,Mechanism of Tyrosine Kinase Receptors,Activated Ras then causes the activation of a cellular kinase cal

4、led Raf-1,Mechanism of Tyrosine Kinase Receptors,Raf-1 kinase then phosphorylates another cellular kinase called MEK. This cause the activation of MEK,Mechanism of Tyrosine Kinase Receptors,Activated MEK then phosphorylates another protein kinase called MAPK causing its activation. This series of ph

5、osphylating activations is called a kinase cascade. It results in amplification of the signal,Mechanism of Tyrosine Kinase Receptors,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