Problem 3

Background and context

Cytokine receptors bind to the JAK protein tyrosine kinase in their cytosolic domains in a very specific and irreversible manner. Initially, in step 1, without ligand, two receptors merge to produce a homodimer, but still, the JAK kinases remain inactive. Once the ligand is bound to the JAK kinase motifs, a conformational shift occurs that draws the domain's close. The JAK domains then phosphorylate one another on a tyrosine residue in an area known as the activation loop, thereby stimulating the kinase and this occurs in step 2. The phosphorylation of numerous tyrosines in the receptor's cytosolic domain occurs as a result of the active JAK kinases and this step 3. The phosphotyrosines formed as a consequence of this process serve as docking regions for signal-transducing proteins, such as the STAT protein.