Article

A Global Protein Kinase and Phosphatase Interaction Network in Yeast

Centre for Systems Biology, Samuel Lunenfeld Research Institute, 600 University Avenue, Toronto, Ontario, M5G 1X5, Canada.
Science (Impact Factor: 31.48). 05/2010; 328(5981):1043-6. DOI: 10.1126/science.1176495
Source: PubMed

ABSTRACT The interactions of protein kinases and phosphatases with their regulatory subunits and substrates underpin cellular regulation.
We identified a kinase and phosphatase interaction (KPI) network of 1844 interactions in budding yeast by mass spectrometric
analysis of protein complexes. The KPI network contained many dense local regions of interactions that suggested new functions.
Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated
protein kinase signaling, the DNA damage response, and metabolism, whereas interactions of the target of rapamycin complex
1 (TORC1) uncovered new effector kinases in nitrogen and carbon metabolism. An extensive backbone of kinase-kinase interactions
cross-connects the proteome and may serve to coordinate diverse cellular responses.

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    • "In this context, it is noteworthy that treatment of yeast cells with the TORC1 inhibitor rapamycin specifically increases ubiquitylation of Npr2. Moreover, all subunits of the SEA complex (except for Sec13) appear to be phosphorylated (Albuquerque et al., 2008; Breitkreutz et al., 2010; Spielewoy et al., 2010) and ubiquitylated (Hitchcock "
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    • "Subsequent studies in yeast also characterized more factors and also signaling pathways such as RAS2 and the TOR signaling pathway (Butow and Avadhani, 2004; Kirchman et al., 1999; Liu and Butow, 2006) (Table 1). The TOR pathway has also being linked to Rtg proteins in the context of retrograde signaling (Breitkreutz et al., 2010; Dilova et al., 2004; Dilova et al., 2002; Giannattasio et al., 2005; Komeili et al., 2000). Furthermore, yeast studies have shown that dysfunctional mitochondria inhibit TORC1 (Kawai et al., 2011). "
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    • "In some cases, pathway crosstalk may be sustained by single proteins [13] through molecular switches provided by post-translational modifications. Namely, different phosphorylation events may lead to inhibition or activation of the target protein and consequently potentially inhibit one pathway and activate another. "
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