Cytoplasmic tyrosine kinases are critical conveyers of extracellular signals. As an example, the JAK - STAT pathway is a relatively well characterized signalling cascade that is activated via a plethora of cytokines and growth factors. This pathway is known to play a role in the regulation of cell proliferation, differentiation, chemotaxis and apoptosis and is important for haematopoiesis, and immune development.

The Janus kinase family consists of 4 distinct family members: JAK 1, JAK 2, JAK3 and TYK2. Whereas JAK 1, JAK2 and TYK2 are ubiquitously expressed, the expression of JAK3 is leukocyte specific. Upon receptor engagement, the Janus kinases are brought into close proximity to one another and are activated via trans-phosphorylation. Activation of these kinases results in the subsequent phosphorylation of tyrosine specific moieties on a number of proteins like and the STAT proteins (Signal Transducers and Activators of Transcription). Currently, 7 different members of the STAT family have been identified; STAT 1, 2, 3 , 4, 5a, 5b, and 6 respectively.

Upon phosphorylation on a conserved tyrosine residue located within the C-terminus, the STAT proteins dimerize and subsequently translocate to the nucleus; translocation has been demonstrated to be dependent upon importin a5 and the Ran nuclear import pathway. Within the nucleus, these proteins bind to and either activate or repress specific gene transcripts.

The JAK-STAT pathway is subject to a number of mechanisms that participate to negatively regulate the pathway; these include for example down-regulation of the receptor, dissociation of the JAKs with its receptor, Suppressors of Cytokine Signaling (SOCS), Protein Inhibitors of STATs (PIAS) as well as Protein Tyrosine Phosphatases (PTPs) like CD45.

Interestingly, mutations in these kinases have been reported to occur in certain leukemic conditions. For instance, V617F has been demonstrated to render haemopoietic cells more sensitive to growth factor.