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JAK/STAT Signaling Pathway

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Growth Hormones Growth Hormones Receptors Cytokines or Growth Factor Cytokines or Growth Factor Receptor Feedback Inhibition JAK2 SHC1 GRB2 SOCS SOCS, CISH CISH ,Pim-1 c-Myc Cytokines Growth Factors RAS p120 Ras-GAP RAF MAP2K1/2 PI3K MTOR MCL1 MCL1, Apoptosis ERK1/2 JAKs SOCS3 SH-PTP2 SH-PTP1 JAKs JAK2 c-SRC STATs STATs STATs STATs STATs STATs STAT5 STAT5 STAT3 STAT3 STAT3 STAT5 AKT PTP PIAS Gene Expression

JAK-STAT signaling pathway is a signal transduction pathway stimulated by cytokines. Compared with other signaling pathways, this signal transduction pathway is relatively simple. It consists of three components, tyrosine kinase-related receptors, tyrosine kinase JAK and transcription factor STAT. Many cytokines and growth factors transmit signals through JAK-STAT signaling pathways, including interleukin 2-7(IL-2~7), GM-CSF (granulocyte/macrophage colony-stimulating factor), GH (growth hormone), EGF (epidermal growth factor), PDGF (platelet-derived factor), and IFN (interferon). These cytokines and growth factors have corresponding receptors on the cell membrane. A common feature of these receptors is that the receptor itself does not have kinase activity, but has a binding site for the tyrosine kinase JAK the intracellular domain. Upon binding with the ligand, receptors phosphorylate the tyrosine residues of various target proteins the through activation of JAK which combines to them, thus transduce signal from the extracellular to the intracellular. JAK/STAT signaling pathway is involved in many important biological processes such as cell proliferation, differentiation, migration, survival, apoptosis, and immune regulation. In addition, the JAK/STAT signaling pathway also plays an important role in drug treatment of anemia, thrombocytopenia, neutropenia and antiviral, etc.

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