JAK2 (Janus Activating Kinase 2) is a tyrosine kinase of the non-receptor type, that associates with the intracellular domains of cytokine receptors; JAK2 is the predominant JAK kinase activated in response to several growth factors and cytokines such as IL-3, GM-CSF and erythropoietin; it has been found to be constitutively associated with the prolactin receptor and is required for responses to gamma interferon. Ligand binding to a variety of cell surface receptors (e.g., cytokine, growth factor, GPCRs) leads to an association of those receptors with JAK proteins, which are then activated via phosphorylation on tyrosines 1007 and 1008 in the kinase activation loop. Activated JAK proteins phosphorylate and activate STAT (signal transducers and activators of transcription) proteins, which then dimerize and translocate to the nucleus. Once in the nucleus, STAT proteins bind to DNA and modify the transcription of various genes.