In previous posts, we discussed about the role of the kinome in the development of cancer. We will focus today on the JAK/STAT pathway.
The JAK-STAT signaling pathway is one of the most extensively studied signal transduction pathways, involving four Janus kinases (JAKs) (JAK1, JAK2, JAK3, and TYK2) and seven signal transducers and activators of transcription (STATs) (STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B and STAT6).
The pathway is activated by many cytokines and plays major roles in various aspects of immune system biology. Disruption of the normal functioning of JAK/STAT factors has been clearly linked to inflammatory disorders and to both hematologic and solid malignancies. Its role remains to be elucidated for other diseases. Also, the role of each specific JAK and STAT can be different depending on the disease.
Use of validated tools to study the signaling pathways is crucial. If you are working on breast cancer, you can use the FFPE samples in your biobank or from your patients to study JAK2. Or if you are working on interferon-signaling, you may be interested in studying JAK1 expression by ICC/IF. JAK3, on the other side, is rather regulated by interleukin-receptors, and mutations in this gene are associated with autosomal SCID (severe combined immunodeficiency disease).
As for STATs, STAT1 is involved in cell viability in response to different stimuli. STAT2 seems to be involved in blocking the immune response by adenoviruses. STAT6 seems to be involved in Th2 cell differentiation, and the study of its interaction with other proteins may be key to understand some IL-4 mediated biological responses.
Well, this is it for those who already know what targets are relevant in their specific model. If you are not sure about which the main target is, you may need to do some profiling using antibody arrays.
Or even if you are sure about the relevancy of your targets, you may wish to study the mechanism of action of drugs targeting the JAK/STAT pathway, or explore a bit more!
Working on immune system signaling pathways? Please leave your comment!