JAK STAT SIGNALING PATHWAY

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The JAK-STAT signalling pathway is a chain of interactions between proteins in a cell, and is involved in processes such as immunity, cell division, cell death and tumour formation. The pathway communicates information from chemical signals outside of a cell to the cell nucleus, resulting in the activation of genes through a process called transcription. There are three key parts of JAK-STAT signalling: Janus kinases (JAKs), Signal Transducer and Activator of Transcription proteins (STATs), and receptors (which bind the chemical signals).[1] Disrupted JAK-STAT signalling may lead to a variety of diseases, such as skin conditions, cancers, and disorders affecting the immune system.

1. JAK STAT SIGNALING PATHWAY RANA SAHA B.PHARM. NSHM KNOWLEDGE CAMPUS, KOLKATA

2. JAK-STAT signaling pathway The JAK-STAT signaling pathway is a chain of interactions between proteins in a cell, and is involved in processes such as immunity, cell division, cell death and tumor formation. The pathway communicates information from chemical signals outside of a cell to the cell nucleus, resulting in the activation of genes through a process called transcription. There are three key parts of JAK-STAT signaling: Janus kinases (JAKs), Signal Transducer and Activator of Transcription proteins (STATs), and receptors (which bind the chemical signals). Disrupted JAK-STAT signaling may lead to a variety of diseases, such as skin conditions, cancers, and disorders affecting the immune system.

3. Mechanism of signalling JAK- Family of cytoplasmic non-receptor tyrosine kinases which get activated after the binding of a cytokine to the cell-surface cytokine receptor. STAT- Family of transcription factors that become activated when one of the tyrosine residues is phosphorylated by JAK. STAT3 dimers then translocate from the cytoplasm into the nucleus – bind to Interferon-stimulated Response Elements. Cellular responses to dozens of cytokines and growth factors are mediated by the evolutionarily conserved.

4. Ex: Involved in Ig class switching in B Cells following a response to IL-4 which phosphorylates STAT6. Resistance to viral infection by interferons mediated through STAT1. Trans-phosphorylated JAKs then phosphorylate downstream substrates, including both the receptor and the STATs. Activated STATs enter the nucleus and bind as dimers or as more complex oligomers to specific enhancer sequences in target genes, thus regulating their transcription. Responses include proliferation, differentiation,migration , apoptosis, and cell survival.

5. Essential for numerous developmental and homeostatic processes, including hematopoiesis , immune cell development, stem cell maintenance, organismal growth, and mammary gland development. Human JAK mutation s cause numerous diseases, including SCID, hyper IgE syndrome, certain leukemias , polycythemia vera , and other myeloproliferative disorders. Small molecular weight cell membrane-permeable drugs that target this pathways have been developed for leukemia therapy. (JAK Inhibitors)

6. Mechanism of signaling