Mitogen-activated protein kinase

The mitogen-activated protein kinase (MAPK) pathway.^{[1][2][3][4][5][6][7][8][9][10]}

Mitogen-activated protein (MAP) kinases (EC 2.7.11.24) are serine/threonine-specific protein kinases that respond to extracellular stimuli (mitogens) and regulate various cellular activities, such as gene expression, mitosis, differentiation, and cell survival/apoptosis.^[11]

Function

MAPKs are involved in the action of most nonnuclear oncogenes. They are involved in cell response to growth factors such as BDNF or nerve growth factor. Extracellular stimuli lead to activation of a MAP kinase via a signaling cascade ("MAPK cascade") composed of MAP kinase, MAP kinase kinase (MKK, MEKK, or MAP2K), and MAP kinase kinase kinase (MKKK or MAP3K, EC 2.7.11.25).

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.

Groups

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

1. extracellular signal-regulated kinases (ERK1, ERK2). The ERK1/2 (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.
2. c-Jun N-terminal kinases (JNKs), (MAPK8,MAPK9,MAPK10) also known as stress-activated protein kinases (SAPKs).
3. p38 isoforms. (MAPK11, MAPK12(= ERK6), MAPK13, MAPK14) Both JNK 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.
4. ERK5. ERK5 (MAPK7), which has been found recently, is activated both by growth factors and by stress stimuli, and it participates in cell proliferation.
5. ERK3/4. ERK3 (MAPK6) and ERK4 (MAPK4) are structurally related atypical MAPKs possessing SEG motifs in the activation loop and displaying major differences only in the C-terminal extension. ERK3 and ERK4 are primarily cytoplasmic proteins which bind, translocate and activate MK5 (PRAK, MAPKAP5). ERK3 is unstable, unlike ERK4 which is relatively stable.^[12]
6. ERK7/8. (MAPK15) This is the newest member of MAPKs and behaves like atypical MAPKs. It possesses a long C terminus similar to ERK3/4.

See also

• MAPK/ERK pathway
• Anthra(1,9-cd)pyrazol-6(2H)-one - inhibitor
• MAPK1
• MAPK3
• MAPK14

References

External links

• Table of names for mitogen-activated kinases.
• MAPK cascade picture
• MeSH Mitogen-Activated+Protein+Kinases
• Mitogen-Activated Protein Kinase Cascades
• Model of MAPK ultrasensitivity in BioModels Database