(MAPKKK) (MAPKK) (MAPK)

MAP kinase activation
Mitogen
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MAPKK kinase
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MAPK kinase
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MAP kinase
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further signalling

In cell biology, mitogen-activated protein kinases (MAPKs) () 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. Extracellular stimuli lead to activation of a MAPK via a signaling cascade composed of MAPK, MAPK kinase (MAPKK), and MAPKK kinase (MAPKKK, ). A MAPKKK that is activated by extracellular stimuli phosphorylates a MAPKK on its serine and threonine residues, and then this MAPKK activates a MAPK through phosphorylation on its serine and tyrosine residues. This MAPK 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

The ERKs (also known as classical MAPKs) 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.

Mitogen-activated protein kinase 1

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Mitogen-activated protein kinase 1 (MAPK1) is also known as "extracellular signal-regulated kinase 2" (ERK2). Two similar (85% sequence identity) protein kinases were originally called ERK1 and ERK2 T. G. Boulton and M. H. Cobb (1991) "Identification of multiple extracellular signal-regulated kinases (ERKs) with antipeptide antibodies" in Cell Regulation Volume 2, pages 357-571. .. They were found during a search for protein kinases that are rapidly phosphorylated after activation of cell surface tyrosine kinases such as the epidermal growth factor receptor. Phosphorylation of ERKs leads to the activation of their kinase activity.

The molecular events linking cell surface receptors to activation of ERKs are complex. It was found that Ras GTP-binding proteins are involved in the activation of ERKs S. J. Leevers and C. J. Marshall (1992) "Activation of extracellular signal-regulated kinase, ERK2, by p21ras oncoprotein" in The EMBO Journal Volume 11, page 569-574. .. Another protein kinase, Raf-1, was shown to phosphorylate a "MAPK kinase", thus qualifying as a "MAPK kinase kinase" J. M. Kyriakis, H. App, X. F. Zhang, P. Banerjee, D. L. Brautigan, U. R. Rapp and J. Avruch (1992) "Raf-1 activates MAP kinase-kinase" in Nature Volume 358, pages 417-421... The MAPK kinase was named "MAPK/ERK kinase" (MEK) C. M. Crews and R. L. Erikson (1992) "Purification of a murine protein-tyrosine/threonine kinase that phosphorylates and activates the Erk-1 gene product: relationship to the fission yeast byr1 gene product" in Proceedings of the National Academy of Sciences of the United States of America'' Volume 89, pages 8205-8209. ..

Receptor-linked tyrosine kinases, Ras, Raf, MEK and MAPK could be fitted into a signaling cascade linking an extracellular signal to MAPK activation T. Itoh, K. Kaibuchi, T. Masuda, T. Yamamoto, Y. Matsuura, A. Maeda, K. Shimizu and Y. Takai (1993) "A protein factor for ras p21-dependent activation of mitogen-activated protein (MAP) kinase through MAP kinase kinase" in Proceedings of the National Academy of Sciences of the United States of America Volume 90, pages 975-979. .. See: MAPK/ERK pathway.

Transgenic gene knockout mice lacking MAPK1 have major defects in early development Y. Yao W. Li, J. Wu, U. A. Germann, M. S. Su, K. Kuida and D. M. Boucher (2003) "Extracellular signal-regulated kinase 2 is necessary for mesoderm differentiation" in Proceedings of the National Academy of Sciences of the United States of America Volume 100, pages 12759-12764. ..

Mitogen-activated protein kinase 3

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Mitogen-activated protein kinase 3 (MAPK3) is also known as "extracellular signal-regulated kinase 1" (ERK1). Transgenic gene knockout mice lacking MAPK3 are viable and it is thought that MAPK1 can fulfill most MAPK3 functions in most cells G. Pages, S. Guerin, D. Grall, F. Bonino, A. Smith, F. Anjuere P. Auberger and J. Pouyssegur (1999) "Defective thymocyte maturation in p44 MAP kinase (Erk 1) knockout mice" in ''Science Volume 286, pages 1374-1377. .. The main exception is in T cells. Mice lacking MAPK3 have reduced T cell development past the CD4⁺CD8⁺ stage.

External links

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• Table of names for mitogen-activated kinases.

References

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Protein kinases | Signal transduction | EC 2.7.11

MAP-Kinase-Weg