MAP cascade

Figure 10.6 Schematic representation of the mitogen-activated protein kinase (MAP) cascades in mammalian cells. (From Voet and Voet, 2004. Reproduced with permission from John Wiley Sons., Inc.)...

The cell cycle encompasses so many different processes that it is clearly impossible to describe it by the single diagram of Fig. 11-15 or by the text written here. The cycle is influenced by a host of growth factors and external stimuli, many of which act on transcription of cyclins and other essential proteins. Transcription factors such as those of the Fos / Jim (AP-1) family in response to the MAP cascade (Fig. 11-13) are among those that control the transcription of cyclins.262 263c However, during mitosis most transcription of any genes is repressed 264... 

Aldehydes undergo a Mukaiyama-aldol reaction followed by a Prins cyclization with the highly reactive allylsilane 329 to afford jy -2,6-tetrahydropyrans 330 that feature an oeo-methylene group at C-4 (Equation 140, Table 12). This Mukaiyama-aldol-Prins (MAP) cascade cyclization has been used to form a key bis-tetrahydropyran intermediate during the total synthesis of leucascandrolide A <2001JA8420>. Similarly, titanium tetrabromide mediated MAP reactions afford 4-bromo tetrahydropyrans <20030L3163>. 

FIGURE 10.6 Schematic representation of the mitogen-activated protein kinase (MAP) cascades in mammalian cells. 

Kopecky and Rychnovsky also targeted leucascandrolide A to demonstrate their Mukaiyama Aldol-Prins (MAP) method (Scheme 38) [78]. The MAP reaction generates an oxocarbenium intermediate from an enol ether and an aldehyde, which is capable of imdergoing a Prins cyclization with the pendant allylsilane. Aldehyde 278 (from Scheme 73, Eq. 1) in the presence of enol ether 142 and boron trifluoride etherate underwent the MAP cascade without incident. The reaction mixture was treated with sodium borohydride to reduce any of the unreacted aldehyde and simplify purification. Desired alcohol 143 was then isolated in 78 % yield as a 5.5 1 mixture of diastereomers. 

The duration of signaling influences how a cell responds to a particular stimulus. For example, brief activation of the MAP kinase cascade in the neuronal cell line, PCI 2, results in proliferation, while sustained... 

Immune Defense JAK-STAT Pathway PIAS proteins Map Kinase Cascades Toll-like Receptors Growth Factors... 

Stimulation of the insulin receptor results in the activation of two major pathways [3] (i) the mitogen-activated protein (MAP) kinase cascade (discussed in chapter MAP kinase cascade) and (ii) the phospha-tidylinositol 3-kinase (PI 3-kinase) pathway which has been extensively studied in the context of the metabolic responses to insulin (summarized in Table 1 and Fig. 2). 

MAPK cascades are composed of three cytoplasmic kinases, the MAPKKK, MAPKK, and MAPK, that are regulated by phosphorylation (Fig. 1) [1, 2]. The MAPKKK, also called MEKK for MEK kinase, is a serine/threonine kinase. Selective activation of MAPKKKs by upstream cellular stimuli results in the phosphorylation of MAPKK, also called MEK for MAP/ERK kinase by the MAPKKK. MAPKKK members are structurally diverse and are differentially regulated by specific upstream stimuli. The MAPKK is phosphorylated by the MAPKKK on two specific serine/ threonine residues in its activation loop. The MAPKK family members are dual specificity kinases capable of phosphorylating critical threonine and tyrosine residues in the activation loop of the MAPKs. MAPKKs have the fewest members in the MAPK signaling module. MAPKs are a family of serine/threonine kinases that upon activation by their respective MAPKKs, are capable of phosphorylating cytoplasmic substrates as well as... 

MAP Kinase Cascades. Figure 1 Organization of MAPK cascades. See text for details. 

MAP Kinase Cascades. Table 1 Pharmacological Inhibitors of MAPK Cascades... 

Mitogen activated protein kinase. MAP Kinase Cascade... 

Neurotrophins (NGF brain-derived neurotrophic factor, BDNF neurotrophin-3, NT-3 NT-4 NT-6) are important regulators of neural survival, development, function, and plasticity of the vertebrate nervous system [1]. Neurotrophins generally function as noncovalently associated homodimers. They activate two different classes of receptors, through which signaling pathways can be activated, including those mediated by Ras and members of the cdc42/rac/rho G protein families, MAP kinase, PI-3 kinase, and Jun kinase cascades. 

The classical PTPs can be subdivided into receptorlike PTPs and nonreceptor, cytosolic PTPs. The second category of PTPs are broadly defined as dual specificity phosphatases (DSPs), which dephosphorylate pSer/ pThr as well as pTyr. MAP kinase phosphatases (MKPs) ( MAP kinase cascades) and PTEN are examples of DSP family members. Remarkably, PTEN also has lipid phosphatase activity that is specific for phosphatidylinositol-3,4,5-trisphosphate generated in response to the actions of PI3K. Finally, the class of low molecular mass (LM-) PTPs and that of CDC25 PTPs accomplish the cells repertoire of PTPs (Fig. 3). 

Activated Ras triggers signalling down the Raf-MEKl / 2-Erkl/2-RSKl MAP kinase cascade. This process is inhibited by the RasGAP neurofibromin (NF1). Both Erkl/and RSK1 can directly phosphorylate TSC2 and these phosphorylation events inhibit the GAP activity of TSC2 and thus ultimately promote mTORCl activity. 

Ludwig S (2007) Influenza viruses and MAP kinase cascades - novel targets for antiviral intervention, Signal Transduction 7 81-88... 

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