The Negative Regulation of JAK/STAT Signaling

摘要: Publisher Summary Cytokines are a large family of protein messengers, which classified into four families based on their structures: hematopoietin, interferon, chemokine, and tumor necrosis factor (TNF). These proteins elicit diverse cellular responses upon binding to cognate transmembrane receptors that expressed the surface target cells. Typically, intracellular portions hematopoietin lack any intrinsic kinase activity therefore dependent receptor-associated effectors, such as Janus kinases (JAKs), initiate signaling pathways. Due importance JAK tyrosine phosphorylation for signal transduction, especially within activation loop, it follows dephosphorylation residues is mechanism employed cell downregulate activity. SHP-1 key negative regulator receptor in hematopoietic epidermal cells, has been implicated dephosphorylating EPO, interleukin-3 (IL-3), granulocyte colony-stimulating (G-CSF), factor-1 (CSF-1), Kit ligand/stem (SCF), growth (EGF), members, JAK1 JAK2. Intrinsic attenuated by intramolecular interactions between catalytic domain (JH1) adjacent, catalytically inactive pseudokinase