Tyrosine Receptor Kinases

Question 1

Receptor tyrosine Kinase

Answer 1

Many growth factors operate by a signalling pathway that includes a multifunctional transmembrane protein called a receptor tyrosine kinase.

Receptor, Transducer, and effector functions are all found in a single membrane protein.

Question 2

Autophosphorylation

Answer 2

When two receptor molecules associate, each tyrosine kinase domain catalyzes the phosphorylation of specific tyrosine residues of its partner.

The activated tyrosine kinase then catalyzes phosphorylation of certain cytosolic protiens, setting of a cascade of events in the cell.

Question 3

After autophosphorylation

Answer 3

Binding sites for proteins with SH2 domains are formed, Grb2 with SOS attatched is one of these proteins. Once it binds to the receptor complex SOS is activated.

Question 4

After SOS is activated

Answer 4

SOS is a release protein, and after it is activated it causes certain G proteins to release GDP and exchange it for GTP. Ras is one of these proteins, when it has GTP bound to it, it becomes active.

Question 5

Activated Ras

Answer 5

Causes the activation of a cellular kinase called raf-1

Question 6

Raf 1

Answer 6

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

Question 7

Activated MEK

Answer 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.

Question 8

Then finally…

Answer 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.