MAP kinase pathway

Anthrax toxin Lethal factor Lethal factor MEKs Endoprotease Increase in intracellular cAMP Inhibition of MAP-kinase pathways Calmodulin dependent adenylylcyclase... 

Adaptor protein, containing one SH2 and two SH3 domains, which assembles signaling complexes at receptors. Particularly important for activation of the Ras-MAP kinase pathway. 

Pearson G, Robinson F, Gibson TB et al (2001) Mitogen-activated protein (MAP) kinase pathways regulation and physiological functions. Endocrine Rev 22 153-183... 

Figure 38-7. Activation of elF-4E by insulin and formation of the cap binding elF-4F complex. The 4F-cap mRNA complex is depicted as in Figure 38-6. The 4F complex consists of elF-4E (4E), elF-4A, and elF-4G. 4E is inactive when bound by one ofa family of binding proteins (4E-BPs). Insulin and mitogenic factors (eg, IGF-1, PDGF, interleukin-2, and angiotensin II) activate a serine protein kinase in the mTOR pathway, and this results in the phosphorylation of 4E-BP. Phosphorylated 4E-BP dissociates from 4E, and the latter is then able to form the 4F complex and bind to the mRNA cap. These growth peptides also phosphorylate 4E itself by activating a component of the MAP kinase pathway. Phosphorylated 4E binds much more avidly to the cap than does nonphosphorylated 4E.

Lee C, Tomkowicz B, Freedman BD, Collman RG. HIV-1 gpl20-induced TNF-a production by primary human macrophages is mediated by phosphatidylinositol-3 (PI-3) kinase and mitogen-activated protein (MAP) kinase pathways. J Leukoc Biol 2005 78(4) 1016-1023. 

The importance of FAK is underlined by the finding that cells expressing a constitutively active form survive in suspension even though they are homeless. Here, the protein kinase is active regardless of the failure to make contact with an extracellular matrix. Rescue from apoptosis also occurs when cells express constitutively activated oncogenic forms of Ras or Src and thus activate Plj-kinase and the MAP kinase pathway. Unlike FAK, these not only prevent apoptosis but also promote proliferative signals that result in tumor formation. 

Gross SD, Schwab MS, Lewellyn AL, Mailer JL 1999 Induction of metaphase arrest in cleaving Xenopus embryos by the protein kinase p90Rsk. Science 286 1365—1367 Gross SD, Schwab MS, Taieb FE, Lewellyn AL, Qian Y-W, Mailer JL 2000 The critical role of the MAP kinase pathway in meiosis II in Xenopus oocytes is mediated by p90Rsk. Curr Biol 10 430-438... 

The results show that CSF activity fluctuates after oocyte activation. Inactivation of CSF proceeds in two steps first, CSF is transiently down-regulated by a mechanism independent from Mos degradation and MAP kinase inactivation to allow exit from the M II arrest. Second, the disappearance of CSF activity after the transition to the first embryonic cell cycle requires inactivation of the MAP kinase pathway. 

Mailer We think S phase suppression after anaphase I is just a secondary effect of having significant Cdc2 kinase activity still around. The MAP kinase pathway is unable to suppress S phase in the absence of cyclin B. 

Lewis TS et al. Identification of novel MAP kinase pathway signaling targets by functional proteomics and mass spectrometry. Mol Cell 2000 6 1343-1354. 

Figure 7.1 Major signaling pathways relevant to this chapter. Simplified schematic diagram of the major signaling pathways which impinge on mRNA translation I. The phosphatidylinositide 3-kinase (PI 3-kinase) pathway II/III. MAP kinases, especially the classical MAP kinase (ERK) pathway and the p38 MAP kinase pathway IV. The mammalian target of rapamycin (mTOR) pathway. Strictly, this diagram shows the rapamycin-sensitive events linked to mTORCl. Selected inhibitors and their sites of action are shown. A numberof components and cross-connections have been omitted for clarity.

Wang, X., Flynn, A., Waskiewicz, A. J., Webb, B. L. J., Vries, R. G., Baines, I. A., Cooper, J., and Proud, C. G. (1998). The phosphorylation of eukaryotic initiation factor eIF4E in response to phorbol esters, cell stresses, and cytokines is mediated by distinct MAP kinase pathways. J. Biol. Chem. 273, 9373-9377. 

Kong AN, Owuor E, Yu R, Hebbar V, Chen C, Hu R and Mandlekar S. 2001. Induction of xenobiotic enzymes by the MAP kinase pathway and the antioxidant or electrophile response element (ARE/EpRE). Drug Metab Rev 33(3-4) 255-271. 

Signal transduction (control of growth factor and MAP-kinase pathways)... 

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