Tyrosine Kinase Associated Receptor and JAK-STAT Pathway
Tyrosine Kinase Associated Receptor
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.
JAK-STAT Pathway
Under resting state: Receptors exist as monomers.
Binding of the ligand with the receptor
↓
Receptors associate to form a dimer
↓
Dimerization increases affinity for JAK
↓
JAKs associate with receptor
↓
JAK get activated
↓
JAKs phosphorylate tyrosine residues on each other and on receptor molecules
↓
Formation of phosphotyrosine residues
↓
STAT (Signal Transducers and Activators of Transcription) binds with phosphotyrosine residues
↓
JAK phosphorylates STAT
↓
STATs dissociate from the receptor and form a dimer
↓
Dimer goes to the nucleus
↓
Regulates gene transcription
↓
Response