JAK STAT Signaling | The Cell Pathway in Physiology, Disease and Death
JAk stands for Janus kinase and the STAT for signal transducers and activator of transcription (JAK/STAT).
In mammals, the JAK/STAT pathway is the fundamental signaling mechanism for a big selection of cytokines and growth factors.
JAK STAT signalling Pathway Mechanism
The tyrosine kinase activity of Janus kinase is activated when the regulatory molecule binds and brings two receptor molecules together to form the dimer. Receptor dimerization brings the two JAKs into proximity, where they can phosphorylate each other. Phosphorylation further activates JAK, allowing it to phosphorylate the receptor.
The tyrosine kinase interest of JAK is activated at the same time as the regulatory molecule binds and brings receptor molecules collectively to form a dimer. Receptor dimerization brings the two JAKs into proximity, wherein they could phosphorylate every other. Phosphorylation similarly turns on JAK, allowing it to phosphorylate the receptor.
The phosphotyrosine residues at the receptor proteins are binding sites for STAT proteins. The STAT proteins are taken into consideration as latent transcription factors. “Latent” means, they are always present in the cytoplasm but are programmed to be activated by using JAK.
STAT binds to the receptor, that brings it right into a role where it may be phosphorylated with the resource of JAK. Once phosphorylated, STATs can then shape a STAT dimer (every STAT molecule binds to the phosphotyrosine of the other phosphorylated STAT). The STAT dimer is a vital transcription issue.
It travels to the nucleus in which it binds to unique sequences inside the DNA. Inactivation takes vicinity while phosphatases cast off phosphate groups from various proteins within the signaling pathway.
List of cytokines acting through JAK-STAT
Cytokines are important defense component of body innate immunity.
IFN-gamma: This comes under the category of cytokines which activates the macrophage in a disease condition
IFN-alpha, IFN-beta: These cytokines are activated mainly in case of viral infections and have an antiviral effect of limiting the spread and growth of the virus.
IL-2: This cytokine responsible for the proliferation of lymphocytes in immune response pattern.
Drug acting on the JAK-STAT pathway
JAK inhibitors are the drugs which hinder the kinase activity of JAK. There are two drugs approved by FDA.
Ruxolitinib has been approved to treat a myeloproliferative disorder.
Tofacitinib is one of the JAK inhibitors that has been approved for the treatment of rheumatoid arthritis.