Together, the JAKs and STATs comprise a simple intracellular signal relay that can be activated by a number of extracellular factors. In vertebrates, the cytokines are the largest class of molecules to utilize the cascade. Although the cytokines have significantly different amino acid sequences, they are divided into two categories on the basis of their structures. The receptors for these molecules are heteromultimeric subunits, with many cytokines using a common subunit in the receptor complex. The first step in activation is binding of the extracellular ligand to the appropriate transmembrane receptor.
Ligand binding typically induces receptor dimerization or multimerization.
Current models hold that receptor dimerization brings their associated JAK molecules into close proximity to each other, presumably facilitating trans-phosphorylation of the JAKs. Inactive STATs are found in the cytoplasm and, upon JAK activation, are recruited to the inner surface of the cell membrane. Here, they are tyrosine phosphorylated by the JAKs, then translocate to the nucleus and bind specific DNA sequences to regulate transcription. Drosophila hop was originally identified as a gene involved in embryonic pattern formation. This same embryonic phenotype is also seen in animals derived from females that lack stat92E gene activity.