Overview of MAPK Signaling

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The MAPK pathway can be activated by an assortment of extracellular stimuli such as growth factors, cytokines, and stress signals. Pathway activation leads to the coordination of a wide variety of cellular responses involving gene expression, proliferation, survival and apoptosis, metabolism, and differentiation. In mammals, there are five distinct groups of MAPKs: the extracellular signal-regulated kinases (ERKs), the c-Jun amino-terminal kinases (JNKs), the p38 isoforms, ERKs 3 and 4, and ERK5 (reviewed in 1). Downstream responses from ERK1/2 activation result mainly in the activation of transcription that promotes cell proliferation. The second group of MAPKs consists of the p38 isoforms.  The. Downstream targets of the p38 isoforms include transcription factors such as ATF1 and -2, NFkappaB, p53, and Elk-1 and several MAPK-activated kinases (MKs).  p38 appears to be critical for immune function and ultimately regulates the expression of many cytokines, transcription factors, and cell surface receptors. The third group consists of the JNKs (JNK1, -2, and -3) which are activated by the MAPKs, MEK4 and MEK7. In response to a variety of stimuli including DNA-damaging agents, cytokines, growth factors and growth factor deprivation, JNK signaling phosphorylates transcription factors such as c-Jun, ATF-2, JunD, and STAT3. ERK3 and ERK4 are structurally related atypical MAPKs. The physiological role of ERK3 and ERK4 is not completely understood, but studies suggest a prominent role in development. The best known substrate for ERK3 and -4 is PRAK (MK5)2. The last group involves ERK5. ERK5 has been found to play an important role in cardiovascular development and neural differentiation.  It is activated by the MAPKK, MEK5, which is activated by the upstream MAPKKKs, MEKK2 and MEKK3. Activated ERK5 phosphorylates substrates such as myocyte enhancer factor 2 (MEF2) and Nur773 .

 

Detection of human ERK5 by WB of immunoprecipitates from HeLa lysate.

Detection of human ERK5 by WB of immunoprecipitates from HeLa lysate. Antibodies: Rabbit anti-ERK5 (A302-655A & A302-656A). Secondary: ReliaBLOT® reagents (WB120).

Detection of human MEK2 by WB of immunoprecipitates from HeLa lysate.

Detection of human MEK2 by WB of immunoprecipitates from HeLa lysate. Antibodies: Rabbit anti-MEK2 (A302-142A & A302-141A). Secondary: ReliaBLOT® reagents (WB120).

Below is the current listing of Bethyl antibodies involved in MAPK signaling pathway research:

 

References

1. P. P. Roux and J. Blenis, Microbiol.Mol Biol Rev. 68, 320-344 (2004).

2. S. Kant et al., J Biol Chem. 281, 35511-35519 (2006).

3. S. Nishimoto and E. Nishida, EMBO Rep. 7, 782-786 (2006).