MAP-kinase

E. G protein-conpled receptors /3-Adrenergic receptor kinase (BARK) Rhodopsin kinase II. Ser/Thr/Tyr protein kinases MAP kinase kinase (MAPK kinase) —TEY— phosphorylation by... 

The fact that the aliosterically preferred conformation may be relatively rare in the library of conformations available to the receptor may have kinetic implications. Specifically, if the binding site for the modulator appears only when the preferred conformation is formed spontaneously, then complete conversion to alios terically modified receptor may require a relatively long period of equilibration. For example, the allosteric p38 MAP kinase inhibitor BIRB 796 binds to a conformation of MAP kinase requiring movement of a Phe residue by 10 angstroms (so-called out conformation). The association rate for this modulator is 8.5 x 105 M-1 s-1, 50 times slower than that required for other inhibitors (4.3 x 107 M 1 s-1). The result is that while other inhibitors reach equilibrium within 30 minutes, BIRB 376 requires 2 full hours of equilibration time [8],... 

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... 

MAP kinase signaling promotes differentiation ofPC12 cells. Adaptor proteins are able to regulate the time course of signaling events, and therefore the cellular outcome. 

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

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

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. 

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). 

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

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

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

Mitogen activated protein kinase. MAP Kinase Cascade... 

Activation of Mi, M3, and M5 mAChRs does not only lead to the generation of IP3 followed by the mobilization of intracellular Ca2+, but also results in the stimulation of phospholipase A2, phospholipase D, and various tyrosine kinases. Similarly, M2 and M4 receptor activation does not only mediate the inhibition of adenylyl cyclase, but also induces other biochemical responses including augmentation of phospholipase A2 activity. Moreover, the stimulation of different mAChR subtypes is also linked to the activation of different classes of mitogen-activated protein kinases (MAP kinases), resulting in specific effects on gene expression and cell growth or differentiation. 

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. 

Activation of inwardly rectifying potassium channels Activation of MAP kinase... 

KC706 Inhibitor enzyme conformation MAP kinase p38a Inflammatory diseases Phase II... 

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). 

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