Systems biology analysis of G protein and MAP kinase signaling in yeast

Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599-7365, USA.
Oncogene (Impact Factor: 8.46). 06/2007; 26(22):3254-66. DOI: 10.1038/sj.onc.1210416
Source: PubMed


Approximately a third of all drugs act by binding directly to cell surface receptors coupled to G proteins. Other drugs act indirectly on these same pathways, for example, by inhibiting neurotransmitter reuptake or by blocking the inactivation of intracellular second messengers. These drugs have revolutionized the treatment of human disease. However, the complexity of G protein signaling mechanisms has significantly hampered our ability to identify additional new drug targets. Moreover, today's molecular pharmacologists are accustomed to working on narrowly focused problems centered on a single protein or enzymatic process. Here we describe emerging efforts in yeast aimed at identifying proteins and processes that modulate the function of receptors, G proteins and MAP kinase effectors. The scope of these efforts is far more systematic, comprehensive and quantitative than anything attempted previously, and includes integrated approaches in genetics, proteomics and computational biology.

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Available from: Henrik G Dohlman, Jun 27, 2014
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    • "It describes an organism's response to an external perturbation by returning state variables to their original values before perturbation. For example, perfect adaptation has been reported in bacterial (e.g., E. coli) chemotaxis (Berg and Tedesco, 1975; Alon et al., 1999; Yi et al., 2000; Hansen et al., 2008), osmotic-stress adaptations (Muzzey et al., 2009), and MAP-kinase regulation (Hao et al., 2007; Mettetal et al., 2008). Such perfect adaption behaviors are thought to be introduced through a time integral on the " controlled variable " in the network , which corresponds to a specific control system structure, i.e., an integral feedback control (Csete and Doyle, 2002). "
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    • "A number of studies have provided mathematical models of ERK activation by EGF (Kholodenko et al, 1999; Orton et al, 2005; Borisov et al, 2009; Kholodenko et al, 2010), including the dynamics of transient and sustained ERK activation (Sasagawa et al, 2005; Nakakuki et al, 2010). ERK response to a G protein-coupled 7TMR in yeast and mammals (Hao et al, 2007; Csercsik et al, 2008) as well as the role of GRK in the desensitization, internalization and recycling of the b 2 adrenergic receptor (b2AR) (Violin et al, 2008; Vayttaden et al, 2010) have also been modeled. In addition, a number of other studies have modeled different aspects of 7TMRs signaling, including calcium signaling (see Linderman, 2009 for a recent review). "
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    • "Sho1p has the potential to form homo-oligomers (Table S1) (Hao et al., 2007). Once exceeding a critical concentration, these oligomers might condense the isolated interaction states into a single net (Figure 8C). "
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