Mitogen-activated protein kinase

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MAP kinase activation Mitogen ↓ MAP kinase kinase kinase (MAP3K or MKKK) ↓ MAP kinase kinase (MAP2K or MKK) ↓ MAP kinase ↓ further signalling

In cell biology, mitogen-activated protein (MAP) kinases (EC 2.7.11.24) are serine/threonine-specific protein kinase that respond to extracellular stimuli (mitogens) and regulate various cellular activities, such as gene expression, mitosis, differentiation, and cell survival/apoptosis ^[1]. Extracellular stimuli lead to activation of a MAP kinase via a signaling cascade ("MAPK cascade") composed of MAP kinase, MAP kinase kinase (MKK or MAP2K), and MAP kinase kinase kinase (MKKK or MAP3K, EC 2.7.11.25)^[1]. A MAP3K that is activated by extracellular stimuli phosphorylates a MAP2K on its serine and threonine residues, and then this MAP2K activates a MAP kinase through phosphorylation on its serine and tyrosine residues. This MAP kinase signaling cascade has been evolutionarily well-conserved from yeast to mammals.

To date, four distinct groups of MAPKs have been characterized in mammals:

1. extracellular signal-regulated kinases (ERKs)
2. c-Jun N-terminal kinases (JNKs)
3. p38 isoforms
4. ERK5

MAPK is involved in the action of most nonnuclear oncogenes. It is responsible for cell response to growth factors such as BDNF or nerve growth factor. The ERKs (also known as classical MAP kinases) signaling pathway is preferentially activated in response to growth factors and phorbol ester (a tumor promoter), and regulates cell proliferation and cell differentiation. The JNKs (also known as stress-activated protein kinases; SAPKs) and p38 signaling pathways are responsive to stress stimuli, such as cytokines, ultraviolet irradiation, heat shock, and osmotic shock, and are involved in cell differentiation and apoptosis. And ERK5, which has been found recently, is activated both by growth factors and by stress stimuli, and it participates in cell proliferation.

[edit] External links

• Table of names for mitogen-activated kinases.
• MAPK cascade picture: http://wwwmgs.bionet.nsc.ru/mgs/gnw/genenet/viewer/MAPK%20cascade.html
• http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7601337&dopt=Abstract

[edit] References

1. ^ ^{a b} Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K and Cobb MH. (2001) "Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions" in Endocr Rev Volume 22, pages 153-183. Entrez PubMed 11294822.

Cell signaling
Key concepts    - Ligand | Receptor | Second messenger | Protein kinase | Transcription factor | Cell signaling networks
Pathways    - Apoptosis | Ca2+ signaling | Cytokine signaling | Hedgehog | Integrin signaling | JAK/STAT | Lipid signaling | MAPK/ERK pathway | mTOR | NF-kB | Notch | p53 | TGFβ | Wnt