Tyrosine Kinase Associated Receptor and JAK STAT Pathway of Intracellular Signaling

Tyrosine Kinase Associated Receptor and JAK-STAT Pathway

The receptor itself has no enzymatic activity.
Associate with a separate molecule that has tyrosine kinase activity ⟶ called tyrosine kinase-associated receptor.
Kinases that associate with these receptors are:
- JAK (Janus family)
- Src family
Example: Receptors for:
- Some cytokines e.g. IL-2 to IL-6
- GM-CSF
- Erythropoietin
- Growth hormone
- Prolactin

Tyrosine Kinase Associated Receptor vs Receptor Tyrosine Kinase

Receptor Tyrosine Kinase is a single molecule that works as a receptor as well as tyrosine kinase.
In Tyrosine kinase-associated receptor, the receptor and enzyme are two separate molecules that associate with each other.
Despite this difference, they both work in a similar manner.

Binding of the ligand with the receptor

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Receptors associate to form a dimer

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Dimerization increases affinity for JAK

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JAKs associate with receptor

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JAK get activated

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JAKs phosphorylate tyrosine residues on each other and on receptor molecules

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Formation of phosphotyrosine residues

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STAT (Signal Transducers and Activators of Transcription) binds with phosphotyrosine residues

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JAK phosphorylates STAT

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STATs dissociate from the receptor and form a dimer

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Dimer goes to the nucleus

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Regulates gene transcription

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Response