Receptor Tyrosine Kinases (RTKs)

Receptor Tyrosine Kinases (RTKs) (Definition)

Receptor tyrosine kinases are single past transmembrane proteins.

Receptor tyrosine kinases have

• a signal binding domain on extracellular side when a receptor is located in the plasma membrane

• tyrosine kinase domain on cytosolic side of membrane.

Signal Binding, effect

Receptor tyrosine kinases are activated by a signal binding to extracellular binding domain.

binding of the signal can induce receptor dimerization as represented here by the two interacting receptor molecules.

Cross Phosphorylation and Kinase Activation

When the receptors are bound to signal molecules and in close proximity, the kinase domain of one receptor can phosphorylate a tyrosine in the kinase domain of another receptor in a process called cross phosphorylation.

Phosphorylation of the kinase domain stimulates the kinase activity.

Auto Phosphorylation

The activated tyrosine kinase domains can phosphorylate other tyrosines in the cytosolic region of the receptor, which is called auto phosphorylation.

The activated kinase domain of receptor tyrosine kinases can also phosphorylate tyrosine on other target proteins

Phosphotyrosine Binding Domains

The phosphorylated tyrosine on the intracellular domain of the receptor create binding sites for other proteins.

Proteins that bind phosphorylated receptor tyrosine kinases have specific regions that bind phosphotyrosine.

Two types of phosphotyrosine binding domains are SH2 domains and PTB domains.

The binding of proteins to phosphotyrosine is specific because surrounding amino acids are also involved in the binding interaction.

Summary of Receptor Tyrosine Kinases

In summary, receptor tyrosine kinases at the plasma membrane are activated by binding to an extracellular signal, which can induce receptor dimerization, kinase domain activation, and auto phosphorylation of the receptors.

The phosphorylated tyrosine on the receptor are binding sites for phosphotyrosine binding proteins which can continue the signaling pathway