Receptor Tyrosine Kinase Pathway Steps. Receptor Tyrosine Kinase RTK Structure and Function

Steps in RTK pathway

Receptor Tyrosine Kinase (RTKs) are high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. RTKs are single-pass transmembrane receptors, that bind polypeptide ligands, mainly growth factors, play key roles in processes such as cellular growth, differentiation, metabolism and motility. RTKs are single-pass, type I receptors present in the plasma membrane.

Why the name Receptor Tyrosine Kinase?

RTK has intrinsic enzymatic activity as tyrosine kinase domain. Tyrosine kinase domain specifically phosphorylates tyrosine residues.

Structure of Receptor Tyrosine Kinase (RTK) 

Receptor tyrosine kinases is a transmembrane receptor that anchors into the membrane. 

The structure consists of 

• Extra cellular ligand-binding domain that binds to the lignad
• Intracellular kinase domain that adds phosphate group to tyrosine upon activation by ligand binding.

The ligand-binding domain is made from two receptor complexes that phosphorylate each other in a process called autophosphorylation. RTKs are activated by autophosphorylation. The propagation of the signal in the cytoplasm is triggered. Tyrosine kinase started to phosphorylate intracellular targets. Depending on what response proteins the cell has inside its cytoplasm, the cell would have very different response to the signal.

• Example: Receptor of Insulin hormone is a tyrosine kinase.
• Epidermal growth factor and transforming growth factor α has tyrosine kinase receptor (EGFR)

Steps in Receptor Tyrosine Kinase (RTK) pathway

Step 1: Ligand binding: RTK undergo conformational change upon ligand binding 

Step 2: Dimerization of the receptor: The monomeric units of the receptor come together and dimerises. Dimerization activates tyrosine kinase domains.

Step 3: Dimer Phosphorylation: Intracellular tyrosine kinase domain phosphorylates tyrosine residues (autophosphorylation) which is bound by an intracellular signal protein.

Step 4: Activation of relay proteins: Phosphorylated tyrosine residues activate intracellular signal proteins including second messengers like inositol triphosphate (IP3) and diacylglycerol (DAG).

Watch this summary video on RTK pathway for better understanding

Step 5: Cellular response which include cellular growth, differentiation, change in metabolism regulated by signal transduction regulating proteins like Ras, MAP kinase (MAPK) etc.

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