Extracellular signal-regulated kinases
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Extracellular signal-regulated kinases (ERKs) are widely expressed and are involved in the regulation of meiosis, mitosis, and postmitotic functions in differentiated cells. Many different stimuli, including growth factors, cytokines, virus infection, ligands for heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors, transforming agents, and carcinogens, activate the ERK pathway. [citation needed]
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[edit] Mitogen-activated protein kinase 1
| mitogen-activated protein kinase 1
| |
| Identifiers | |
| Symbol(s) | MAPK1 PRKM2, PRKM1 |
| Entrez | 5594 |
| OMIM | 176948 |
| RefSeq | NM_002745 |
| UniProt | P28482 |
| Other data | |
| Locus | Chr. 22 q11.2 |
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 <ref name="Boulton1991">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. Entrez PubMed 1654126.</ref>. 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 <ref name="Leevers1992">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. Entrez PubMed 1371463.</ref>. Another protein kinase, Raf-1, was shown to phosphorylate a "MAPK kinase", thus qualifying as a "MAPK kinase kinase" <ref name="Kyriakis1992">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.Entrez PubMed 1322500.</ref>. The MAPK kinase was named "MAPK/ERK kinase" (MEK) <ref name="Crews1992"> 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. Entrez PubMed 1381507.</ref>.
Receptor-linked tyrosine kinases, Ras, Raf, MEK and MAPK could be fitted into a signaling cascade linking an extracellular signal to MAPK activation <ref name="Itoh1993">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. Entrez PubMed 8381539.</ref>. See: MAPK/ERK pathway.
Transgenic gene knockout mice lacking MAPK1 have major defects in early development <ref name="Yao2003">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. Entrez PubMed 14566055.</ref>.
[edit] Mitogen-activated protein kinase 3
| mitogen-activated protein kinase 3
| |
| Identifiers | |
| Symbol(s) | MAPK3 PRKM3 |
| Entrez | 5595 |
| OMIM | 601795 |
| RefSeq | NM_001040056 |
| UniProt | P27361 |
| Other data | |
| Locus | Chr. 16 p11.2 |
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 <ref name="Pages1999"> 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.
Entrez PubMed 10558995.</ref>. The main exception is in T cells. Mice lacking MAPK3 have reduced T cell development past the CD4+CD8+ stage.
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[edit] References
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| 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 |
