Chapter 13 : Signal Transduction

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Environmental changes that can alter cellular physiology to which microorganisms must respond to maintain cellular homeostasis include nutrient availability, pH, temperature, osmotic stress, and other microorganisms. In microbial eukaryotes there are several homeostatic systems that contribute to maintaining a constant intracellular environment. These include the small GTPase proteins of the Ras superfamily of proteins, mitogen-activated protein kinase (MAPK) pathway, cyclic AMP (cAMP)-regulated protein kinase (PKA), and the tripartite Gprotein signaling pathways. This chapter discusses the current status of one's understanding of regulatory systems in Aspergillus fumigatus and their role in regulating the physiology of this fungus. It also discusses how these regulatory networks contribute to pathogenesis in A. fumigatus. MAPKs are involved within signaling pathways responsible for individual maintenance and integrity for a range of environmental and nutritional stresses. These MAPK signaling pathways could prove to be potential targets for antifungals, given their central role in governing fundamental homeostatic systems regulating fungal cellular physiology. In summary, major regulatory signaling pathways that regulate fungal cell physiology and contribute to robust hyphal growth are good candidates for pathways that might be exploited in the development of a novel mechanism to inhibit fungal growth in an animal host.

Citation: Gregory S, Taylor S. 2009. Signal Transduction, p 159-167. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch13
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Image of Figure 1.
Figure 1.

Model for the small G-protein activation and inactivation cycle. An activating signal leads to the exchange of GTP for GDP on the G-protein, catalyzed by GEF, producing the active GTP-bound G-protein. Inactivation of the GTP-bound G-protein is catalyzed by GAP, which increases the rate of hydrolysis of GTP to GDP.

Citation: Gregory S, Taylor S. 2009. Signal Transduction, p 159-167. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch13
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Image of Figure 2.
Figure 2.

Model for regulation of PKA. An activating signal leads to dissociation of the tripartite G-protein into the α-subunit and the β-γ dimer. The free α-subunit stimulates adenyl cyclase, leading to increased cAMP levels. cAMP binds to the regulatory subunits (R) of the PKA tetramer, leading to a conformational change. The now-active protein kinase catalytic subunits (C) can then phosphorylate downstream target proteins.

Citation: Gregory S, Taylor S. 2009. Signal Transduction, p 159-167. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch13
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Image of Figure 3.
Figure 3.

Model for the MAPK cascade. An intracellular signal created from upstream activators responding to a receptor-ligand interaction will activate a MAP kinase kinase kinase (MAPKKK), which phosphorylates a MAP kinase kinase (MAPKK), which in turn phosphorylates the MAPK. This MAPK sends a signal to a downstream target, often a transcription factor that will in turn adjust gene expression to meet the requirements of the environment.

Citation: Gregory S, Taylor S. 2009. Signal Transduction, p 159-167. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch13
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