MAPK/ERK pathway



  The MAPK/ERK pathway is a protein components [1]. The basic pathway shown in the figure (to the right) and described below includes the major components of the pathway. In many cell types, activation of this pathway promotes cell division.

Coupling cell surface receptors to G proteins

Receptor-linked small G proteins can be activated in a similar way, but are not discussed further here.

Kinase cascade

Activated Ras activates the protein kinase activity of mitogen-activated protein kinase (MAPK).

Technically, RAF, MEK and MAPK are all mitogen-activated kinases, as is MNK (see below). MAPK was originally called "ERKs) and microtubule-associated protein kinase (MAPK). One of the first proteins known to be phosphorylated by ERK was a microtubule-associated protein. As discussed below, many additional targets for phosphorylation by MAPK were later found and the protein was re-named "mitogen-activated protein kinase" (MAPK). The series of kinases from RAF to MEK to MAPK is an example of a protein kinase cascade. Such series of kinases provide opportunities for feedback regulation and signal amplification.

Regulation of translation and transcription

Three of the many proteins that are phosphorylated by MAPK are shown in the Figure. One effect of MAPK activation is to alter the ribosomal protein S6 kinase (RSK). This activates RSK which in turn phosphorylates ribosomal protein S6 [5]. Mitogen-activated protein kinases that phosphorylate ribosomal protein S6 were the first to be isolated [4].

MAPK regulates the activities of several CREB. MAPK also regulates the transcription of the Fos gene. By altering the levels and activities of transcription factors, MAPK leads to altered transcription of genes that are important for the cell cycle.

See also

References

  1. ^ R. J. Orton, O. E. Sturm, V. Vyshemirsky, M. Calder, D. R. Gilbert and W. Kolch (2005) "Computational modelling of the receptor-tyrosine-kinase-activated MAPK pathway" in The Biochemical journal Volume 392, pages 249-261. Review.Entrez PubMed 16293107.
  2. ^ W. X. Schulze, L. Deng and M. Mann (2005) "Phosphotyrosine interactome of the ErbB-receptor kinase family" in Molecular systems biology Volume 1, May 25.Entrez PubMed 16729043.
  3. ^ N. Zarich, J. L. Oliva, N. Martinez, R. Jorge, A. Ballester, S. Gutierrez-Eisman, S. Garcia-Vargas and J. N. Rojas (2006) "Grb2 Is a Negative Modulator of the Intrinsic Ras-GEF Activity of hSos1" in Molecular Biology of the Cell Epub ahead of print.Entrez PubMed 16760435.
  4. ^ a b J. Avruch, A. Khokhlatchev, J. M. Kyriakis, Z. Luo, G. Tzivion, D. Vavvas and X. F. Zhang (2001) "Ras activation of the Raf kinase: tyrosine kinase recruitment of the MAP kinase cascade" in Recent Progress in Hormone Research Volume 56, pages 127-155. Entrez PubMed 11237210.
  5. ^ M. Pende, S. H. Um, V. Mieulet, M. Sticker, V. L. Goss, J. Mestan, M. Mueller, S. Fumagalli, S. C. Kozma and G. Thomas.(2004) "S6K1,(-/-)/S6K2(-/-) mice exhibit perinatal lethality and rapamycin-sensitive 5'-terminal oligopyrimidine mRNA translation and reveal a mitogen-activated protein kinase-dependent S6 kinase pathway" in Molecular and Cellular Biology Volume 24, pages 3112-3124. Entrez PubMed 15060135.
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Cell physiology: signal transduction

Ion channel gating - MAPK/ERK pathway - Mechanotransduction - Phototransduction - Second messenger systems - Synaptic transmission

 
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