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Activator protein12/27/2022 ![]() Phosphorylation and activation of MAP kinases by MAP kinase kinases occurs on two residues within a tripeptide motif (Thr–Xaa–Tyr) located within the T-loop that controls the conformation of the MAP kinase active site. MAP kinases are activated within conserved protein kinase signaling modules composed of a MAP kinase, a MAP kinase kinase, and a MAP kinase kinase kinase. A second functional similarity between MAP kinases is the mechanism of activation. This substrate specificity is mediated, in part, by the selective docking of MAP kinases to substrate proteins. However, the substrate specificity of individual MAP kinases is different for individual MAP kinase isoforms. For example, MAP kinases phosphorylate substrate proteins on conserved Ser–Pro and Thr–Pro motifs. These enzymes are also functionally related. The MAP kinases are encoded by a group of genes that are related in sequence. Mitogen-activated protein (MAP) kinases are critical mediators of signal transduction in mammalian cells. Davis, in Handbook of Cell Signaling (Second Edition), 2010 Introduction In psoriasis, epidermal sections from psoriatic lesions show elevated levels of activated MAPK and ERK compared with healthy skin. Significantly higher levels of activated MAPK-4 and MAPK-7 were observed in synovial samples from patients with RA compared to patients with osteoarthritis. 10, 11 Activated ERK, JNK, and p38 MAPKs have been detected in synovial tissue isolated from patients with RA but not in synovial tissue isolated from patients with osteoarthritis. The MAPK pathway is activated in RA and psoriasis. 9 Upon receptor activation, MAPKs are activated by sequential phosphorylation of upstream MAPKs and MAPKs. 8 The three groups of MAPKs that have been well characterized include the extracellular signal-regulated kinases (ERKs), the c-Jun N-terminal kinases (JNKs), and the p38 MAPKs. 5–7 MAPKs make up a family of more than 20 serine/threonine kinases. 3, 4 Cytokines that signal through the MAPK pathway include tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-2, IL-6, IL-7, and IL-10. The MAPK pathway is a critical regulator of processes such as cell proliferation, differentiation, growth, and survival. ![]() Fleischmann, in Comprehensive Medicinal Chemistry III, 2017 5.13.1.2.1 MAP kinase pathway
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