The mitogen-activated protein kinase (MAPK) signaling pathway is a typical example of a protein kinase cascade. MAPKs generally form multi-tiered pathways that receive input from several levels above. Typically, a MAPK is activated through phosphorylation by an activated MAP2K, which is activated through phosphorylation by an activated MAP3K. Unlike MAP3Ks, the activation mechanisms of MAPKs and MAP2Ks are relatively simple.
Key MAPK targets include
Learn more about MAPK signaling pathway
Many MAP3Ks require multiple steps for activation, usually involving membrane bound GTPases, homo- and hetero-dimerization of the kinase domains, and trans-phosphorylation of the dimers. Each step in MAPK pathway provides for the amplification and specificity of the signals as they pass through the kinase cascade and eventually activate a number of regulatory molecules in the cytoplasm and nucleus where they initiate cellular processes such as differentiation, proliferation, and development. In addition, many oncogenes have been shown to encode proteins that communicate mitogenic signals upstream of the MAPK cascade. As a result, the MAPK pathway gives a straightforward explanation of the mechanism of action of most nonnuclear oncogenes. Four major MAPK groups participate in relatively distinct pathways. These include the extracellular signal-regulated kinases 1 and 2 (ERK1/MAPK3 and ERK2/MAPK1), c-Jun amino-terminal kinases 1, 2, and 3 (JNK1/MAPK8, JNK2/MAPK9, JNK3/MAPK10), p38-alpha (MAPK14), -beta (MAPK11), -gamma (MAPK12/ERK6), and -delta (MAPK13/SAPK4), and ERK5 families. Additional, atypical MAPKs such as ERK 3/4 (ERK 3 & ERK 4), ERK 7/8 (ERK 7 & ERK 8), and Nemo-like kinase (NLK), have distinct regulation and functions.
MAPK1/ERK2 and MAPK3/ERK1 antibodies
Mitogen activated protein kinase 1 and 3 (MAPK1 and MAPK3) are serine/threonine kinases, activated by dual phosphorylation of tyrosine and threonine residues. This activation is catalyzed by upstream MAP2 kinases, which are ultimately stimulated in response to extracellular stimuli such as mitogens, growth factors, and cytokines. Activated MAPK1 moves to the nucleus where it phosphorylates transcription factors. MAPK1 and MAPK3 share 85 percent identity overall, with even more similarity in their substrate binding regions. The MAPK/ERK cascade mediates biological functions such as cell growth, survival, adhesion, and differentiation by regulating transcription, translation, and cytoskeletal rearrangements.
Mitogen activated protein kinase 8 (MAPK8) is a member of the MAP kinase family. MAPKs regulate a wide variety of cellular processes by transmitting extracellular signals that elicit intracellular responses. MAPK8 is one of three JNK/MAPKs (MAPK8/JNK1, MAPK9/JNK2, and MAPK10/JNK3) that participate in the JNK/SAPK (stress-activated protein kinase) cascade of the MAPK signaling pathway. It is activated by upstream MAP2Ks which are stimulated in response to stress signals that include ultraviolet radiation, oxidative stress, misfolding of endoplasmic reticulum proteins, osmotic shock, and inflammation.
Mitogen activated protein kinase 11 (MAPK11) is one of four isoforms of p38 MAPK: p38-alpha (MAPK14), p38-beta (MAPK11), p38-gamma (MAPK12/ERK6), and p38-delta (MAPK13/SAPK4). Found at its highest levels in the brain and heart, MAPK11 plays an important role in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, by either inducing chromatin remodeling or by recruiting the transcription machinery. It also regulates processes such as rRNA synthesis and cell growth, the elongation of mRNA during translation, protein synthesis, protein turnover, and ectodomain shedding of trans-membrane proteins.
MAPK14/p38 alpha antibodies
Mitogen activated protein kinase 14 (MAPK14) is known as p38-alpha and is one of four isoforms of p38 MAPK: p38-alpha (MAPK14), p38-beta (MAPK11), p38-gamma (MAPK12/ERK6), and p38-delta (MAPK13/SAPK4). MAPK14 is activated in response to a variety of extracellular stimuli including osmotic shock, heat shock, inflammatory cytokines, lipopolysaccharides, anisomycin, UV light, and various growth factors. Through its varied downstream targets, MAPK14 plays an essential role in embryonic development, regulating cellular functions such as proliferation, differentiation, apoptosis, adhesion, and migration. It also regulates the cellular response to stress and influences many metabolic pathways.
ERK3 (MAPK6) is a member of the serine/threonine protein kinase family, and is most closely related to mitogen-activated protein kinases (MAP kinases). MAP kinases, also known as extracellular signal-regulated kinases (ERKs), are activated through protein phosphorylation cascades where they integrate multiple biochemical signals. This kinase is localized in the nucleus, and has been reported to be activated in fibroblasts upon treatment with serum or phorbol esters.
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