The large subgroup of cytokines, the type I and type II cytokine-receptor superfamily, encompasses receptors that bind interferons, many interleukins, and colony stimulating factors use the signaling transduction mechanism: JAK-STAT pathway.
Four JAKs- JAk1, JAK2, JAK3 and tyrosine kinase 2- selectively associate with the cytoplasmic domains of a number of cytokine receptors.
JAK3 and Tyrosine kinase 2 are important in immune responses.
JAK pathway plays a key role in hematopoiesis and immune function.
JAK1 signals proinflammatory cytokines.
JAKs bind to types I and II cytokine receptors and transmit extracellular cytokine signals to activate various signal transducers and activators of transcription, which drive the pro inflammatory cellular immune response.
Eyrthropoietin and thrombopoietin signal primarily through JAK2.
Phosphorylation of JAK2 results in cellular proliferation in the absence of external growth factors, and leads to clonal proliferation of hematopoetic cells.
Activation of JAK pathwy triggers signal transducers and activators of transcription (STATs) to regulate normal inflammatory responses and hematopoiesis.
There are 7 STATs.
JAK pathway is tightly regulated in normal cells by a balance of activators and inhibitors.
JAK pathway has roles in the growth, proliferation, and immunity of cells.
Disruption of the balance in the JAK pathway can contribute to the development and progression of cancer cells and can contribute to inflammation and immunosuppresssion in the tumor microenvironment.