The MAPK signaling cascade

  title={The MAPK signaling cascade},
  author={Rony Seger and Edwin G. Krebs},
  journal={The FASEB Journal},
  pages={726 - 735}
The transmission of extracellular signals into their intracellular targets is mediated by a network of interacting proteins that regulate a large number of cellular processes. Cumulative efforts from many laboratories over the past decade have allowed the elucidation of one such signaling mechanism, which involves activations of several membranal signaling molecules followed by a sequential stimulation of several cytoplasmic protein kinases collectively known as mitogen‐activated protein kinase… 
Alternative Splicing of MAPKs in the Regulation of Signaling Specificity
The role of distinct genes, and the alternatively spliced isoforms of MAPKKs and MAPKs, in the signaling specificity are covered, which indicates that these components play an essential role in determining the proper cell fate in response to distinct stimulations.
The extracellular signal-regulated kinase: Multiple substrates regulate diverse cellular functions
Understanding of these processes may provide a full picture of the distinct, and even opposing cellular processes that are regulated by the ERK cascade, which is described in the current review.
The mitogen-activated protein kinase signaling cascade: from bench to bedside.
The extracellular signal-regulated kinase (ERK) cascade, which was the first MAPK cascade elucidated and is the subject of this review, is described and its activation and regulation is described.
The MAP kinase signaling cascades: a system of hundreds of components regulates a diverse array of physiological functions.
Four MAPK cascades have been identified in the last 20 years and those are usually named according to the MAPK components that are the central building blocks of each of the cascades, and the existence of several distinct components in each tier of the different cascades is described.
The ERK mitogen-activated protein kinase signaling network: the final frontier in RAS signal transduction.
Despite considerable advances in understanding the ERK-MAPK network, the ability of cancer cells to adapt to the inhibition of key nodes reveals a level of complexity that remains to be fully understood.
The ERK cascade
This cascade may serve as a prototype of the other MAPK cascades, and the study of this cascade is likely to contribute to the understanding of mitogenic and other processes in many cell lines and tissues.
Mitogen-activated protein kinases and their role in radiation response.
The MAPK signaling pathways are discussed, which play a major role in regulating cell growth, survival, and differentiation, and their roles in cellular radiation responses.
Activation and signal transduction via mitogen‐activated protein (MAP) kinases in T lymphocytes
This review examines how the activation of several MAP kinases is regulated, their role in signal transduction initiated by a variety of stimuli, and how this may lead to different cellular responses.
Regulation of the MAPK family members: role of subcellular localization and architectural organization.
  • G. Fanger
  • Biology
    Histology and histopathology
  • 1999
This review describes what is currently known about the subcellular localization of MAPK pathway signaling proteins and the relocalization that occurs during events associated with activation of the MAPK family members.


The MAP kinase cascade.
A divergence in the MAP kinase regulatory network defined by MEK kinase and Raf
MEKK was expressed in all mouse tissues tested, and it phosphorylated and activated MEK, independent of Raf, a growth factor-regulated protein kinase that also phosphorylates MEK.
Requirement for integration of signals from two distinct phosphorylation pathways for activation of MAP kinase
It is demonstrated that MAP kinase is only active when both tyrosyl and threonyl residues are phosphorylated and suggested therefore that the enzyme functions in vivo to integrate signals from two distinct transduction pathways.
Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1
Induction of MEKK does not result in the activation of MAPK, but instead stimulates the stress-activated protein kinases (SAPKs)6–8 which are identical to a Jun amino-terminal kinase9,10 which in turn phosphorylates and activates SAPK.
Raf-1 activates MAP kinase-kinase
Results indicate that c-Raf-1 is an immediate upstream activator of MAPK-K in vivo, the first physiological substrate of the c-raf-l protooncogene product to be identified.
Critical tyrosine residues regulate the enzymatic and biological activity of Raf-1 kinase
It is demonstrated that maturation of the tyrosine phosphorylation sites can dramatically alter the function of Raf-1 and this is the first report that a transforming Raf- 1 protein can be generated by a single amino acid substitution.
Dissection of the protein kinase cascade by which nerve growth factor activates MAP kinases
The 'MAP kinase kinases' (MAPKKs) in PC12 cells which are activated by NGF are identified and it is reported that MAPKKs are dependent on serine/threonine phosphorylated for activity and promote phosphorylation of serine-threonines and tyrosine residues on MAPKs.
Ras-dependent growth factor regulation of MEK kinase in PC12 cells.
Ras simultaneously controls the activation of members of the Raf and MEKK families of protein kinases and abolished activation of MEKK and B-Raf by EGF, NGF, and TPA.