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The mitogen activated protein kinases (MAPKs) are a family of signal transduction proteins which convert extracellular signals, such as growth factors and stresses, to the activation of intracellular pathways. The signaling transduction pathways of MAPKs have been highly conserved from yeast to multicellular organisms. In mammals, at least four subfamilies of MAPKs have been described, including the extracellular signal-regulated kinases (ERKs), ERK5, the c-Jun NH2-terminal kinases (JNKs) and the p38 isoforms (p38s). JNK1 and JNK2 are expressed in most tissues, while JNK3 is expressed predominantly in neuronal cells. Among the four p38 MAPK isoforms (p38-α, p38-β, p38-γ, and p38-δ), p38-α and p38-β have been studied most extensively, while p38-δ was recently suggested to play a role in inflammatory and neurodegenerative diseases. ERK1 and ERK2 are the prototypes of the eight isoforms of ERK and are activated by MAPK/ERK kinase (MEK) 1 or 2, whereas ERK5 is specifically activated by a different upstream kinase, MEK5. ERK5 has a uniquely long COOH-terminus that mediates specific functions such as shuttling between the nucleus and cytoplasm. MAPKs are mainly modulated by upstream MAPK kinases (MKKs) and MAPK phosphatases which modify the phosphorylation of the MAPK threonine and tyrosine (T-X-Y) motif.
Figure 1. The MAPK signaling pathways. (a) The MAPK pathways mediate intracellular signaling triggered by extracellular stimuli and by intracellular stimuli. (b) The MAPK signaling pathways are activated through direct interaction between the kinase components or the formation of a signaling complex by various kinases centered on a scaffold protein.
Activated MAPKs catalyze the phosphorylation on specific serine and threonine residues of target substrates and trigger multiple cellular responses, such as proliferation, differentiation, and apoptosis. In consistence with their important roles in cellular processes, MAPKs have been found to play important physiological roles, such as maintaining tissue homeostasis and regulating embryonic development. On the other hand, extracellular stresses can induce MAPK activation in pathological conditions. There are accumulative data suggesting that MAPK activation is critical in regulating inflammation associated cancer development. Compromised MAPK signaling pathways have also been found to play significant roles in the pathogenesis of a wide range of diseases including cancer and neurodegenerative disorders such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS).
The roles of MAPKs in tumor initiation and progression have been well documented. A simple model can be proposed as that the MAPK-mediated inflammation plays a role in the initiation of the tumors, whereas the regulation of cell proliferation, senescence and cell death by MAPKs is important for the progression of the tumors once they are formed. The development of small molecule drugs that selectively inhibit individual components of MAPK signaling pathways is a key therapeutic strategy for cancer and neurodegenerative disorders. Such agents are also probably to prove highly valuable for studying the roles of MAPK pathways in normal physiological processes and in the pathogenesis of human diseases.
Creative Biogene is able to offer a variety of MAPK signaling pathway related products including stable cell lines, viral particles and clones for your drug discovery projects.
MAPK Signaling Pathway Product Panel
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