Signal transduction MAPK

Also mitogen-activated protein kinases (MAPK) are involved in ABA signal transduction. MAPKs are part of signal cascades involving several phosphorylation events and are themselves activated by phosphorylation [40]. The MAPK family is highly conserved between species as different as mammals, yeast and plants. 

Sorafenib is a multitargeted cancer therapy that inhibits VEGFR, PDGFR, KIT, fetal liver tyrosine kinase 3 (FLT-3), and the serine/threonine kinase RAF. RAF kinase is a key downstream effector of Ras in the MAPK/Ras signal-transduction pathway that has been linked to various cancers. Sorafenib is both a tyrosine kinase inhibitor and serine/threonine signal-transduction inhibitor. Sorafenib has been approved in renal cancer. 

The VACM-1 receptor is a membrane-associated protein with a single putative transmembrane domain that binds selectively AVP (XD — 2 nM), but cannot discriminate between VXR and V2R analogues. It is expressed in endothelial and medullary collecting duct cells and upon stimulation by AVP. It induces a mobilization of cytosolic-free Ca2+, decreases cAMP production and inhibits cellular growth via MAPK phosphorylation and p53 expression. The mechanism of action and physiological functions of this new receptor are not well understood, but it seems to participate in the regulation of AVP induced signal transduction pathways or of a yet unidentified peptide. 

Jung, H. W. Chung, Y. S. Kim, Y. S. Park, Y.-K. Celastrol inhibits production of nitric oxide and proinflammatory cytokines through MAPK signal transduction and NF-kB in LPS-stimulated BV-2 microglial cells. Exp. Mol. Med. 2007, 39, 715-721. 

These data indicate that Raf-1 acts downstream of growth factor receptors in the signal transduction cascade. Where Raf-1 acts in this cascade is not clear, but evidence is mounting that indicates it acts downstream of rasl and upstream of MAPKK (reviewed in Roberts, 1992). Although Raf-1 shows no homology to STE11, a S. cerevisiae activator of MAPKK, it can activate both MAPKK and MAPK (Dent et al., 1992 Howe et al., 1992 Kyriakis et al., 1992). 

Some members of this family have been shown to mediate the dephosphorylation of MAPKs under physiological conditions. Others dephosphorylate Cdc-2 and related CDKs. However, relatively little is known to date about the regional distribution of these dual-functioning phosphatases in the brain and the specific function these enzymes serve in the regulation of neuronal signal transduction. Considerable interest has focused on one particular MAPK phosphatase, which can be induced very rapidly, at the level of gene transcription, in target cells in response to cellular activation [44]. 

As mentioned above, activation of TrkA by NGF may result in cellular proliferation, differentiation or survival. Exactly how different TrkA-induced signal transduction mechanisms are translated into each one of these functions is incompletely understood. It has been suggested that proliferation and differentiation are mediated by activation of the MAPK cascade while survival is mediated by activation of PI-3-K. The competing actions of neurotrophins on... 

Eukaryotic ABC transport system Phosphotransferase system (PTS) Ion-coupled transport system Signal Transduction Two-component system Bacterial chemotaxis MAPK signaling pathway Second messenger signaling pathway Ligand-Receptor Interaction G-protein-coupled receptors Ion-channel-linked receptors Cytokine receptors Molecular Assembly Ribosome assembly Flagellar assembly Enzyme assembly... 

Fig. 6. Role of signal transduction pathways in phosphorylating H3 at Ser-10 and Ser-28. The Ras-MAPK (mitogen activated protein kinase) pathway is activated by EGF (epidermal growth factor) and TPA (12-0-tetradecanoylphorbol-13-acetate). UV-B activates both the Ras-MAPK pathway and the p38 kinase pathway (for more information about the signal transduction pathways see http // kinase, oci.utoronto.ca/signallingmap.html).

The MAPK/ERK proteins are at the lower end of signal transduction within a MAPK module and are generally preceded by two other protein kinases (Fig. 10.2). The MAPK/ERK proteins receive the signal in the form of an activating phosphorylation by a preceding protein kinase known as MAP/ERK kinase (MEK) or also MAP kinase kinase (MAPKK). 

The MEK kinases (MAPKK kinases) are Ser/Thr-specific protein kinases and are the entry point for signal transduction in a MAPK module. The best characterized representative, Raf-1 kinase, is activated by Ras protein in its GTP-bound form. Raf kinase phosphorylates downstream MEK proteins at two Ser residues, which are separated by three other amino acids. All known MEK proteins have a similar phosphorylation site in the conserved sequence LID/NSXANS/T (X any amino acid). Other representatives of the MEK kinase group are Mos kinase and the protein kinases MEKKl—3. 

Signal transduction by the Fas-related TNF receptor is of a more complex nature and can mediate both proapoptotic and antiapoptotic signals. In the normal situation, binding of TNF to its receptor initiates a signal chain that activates a MAPK pathway and creates a signal for c-Jim expression. In addition, the IxB-NFxB pathway may be activated. Both NFkB and c-Jim have an antiapoptotic and proliferation-promoting effect. 

The A3 Receptor and the Mitogen-Activated Protein Kinases (MAPKs) Signal Transduction Cascade... 

HIF-la expression and activity are also regulated by phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signal transduction pathways (Zhong et al. 2000 Semenza 2002). 

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