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. 2011 Mar 1;10(5):767-70.
doi: 10.4161/cc.10.5.14828. Epub 2011 Mar 1.

Kelch repeat proteins control yeast PKA activity in response to nutrient availability

Roli Budhwar  1 , Guoqiang Fang, Jeanne P Hirsch
Affiliations

Kelch repeat proteins control yeast PKA activity in response to nutrient availability

Roli Budhwar et al. Cell Cycle. .

Abstract

Regulation of protein kinase A (PKA) by binding of cAMP to the regulatory subunit and the resulting release of the active catalytic subunit is a very well established mechanism of kinase activation. We have shown recently that PKA in budding yeast is also subject to an additional level of regulation that that modulates its activity in response to nutrient availability. Nutrient regulation of PKA activity requires a pair of proteins, Gpb1 and Gpb2, that contain several kelch repeats, a sequence motif that predicts that they fold into a β-propeller structure. The regulatory process mediated by Gpb1 and Gpb2 causes an increase in the stability and phosphorylation of the PKA regulatory subunit Bcy1 in response to low extracellular glucose concentrations. Phosphorylation of serine-145 of Bcy1 controls its stability, and other phosphorylation events at the cluster of serines at positions 74-84 correlate with changes in nutrient availability. Here we present data consistent with a model in which the effects of Gpb1 and Gpb2 on Bcy1 are an indirect consequence of their primary effects on the PKA catalytic subunits.

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Figures

Figure 1
Figure 1
The PKA pathway in Saccharomyces cerevisiae.
Figure 2
Figure 2
(A) Cell lysates were prepared from Tpk analog-sensitive strain Y3527 (tpk1M164G tpk2M147G tpk3M165G) expressing the indicated HA-BCY1 deletions that were untreated or treated with 1 µM 1NM-PP1 for 90 min. Lysates were analyzed by SDS-PAGE and immunoblotting with anti-HA antibody. (B) Schematic diagram of Bcy1 deletion constructs indicating their ability to undergo phosphorylation when PKA is inhibited. Asterisk indicates non-specific band.
Figure 3
Figure 3
Cell lysates were prepared from the following strains grown in 0.05% glucose to log phase: strain HS287-2C (bcy1Δ) carrying plasmids containing wild type HA-BCY1, HA-BCY1S77,79A or HA-BCY1S83,84A (lanes 1, 3 and 5) and strain HS293-10D (gpb1Δ gpb2Δ bcy1Δ) carrying plasmids containing wild type HA-BCY1, HA-BCY1S77,79A or HA-BCY1S83,84A (lanes 2, 4 and 6). Lysates were analyzed by SDS-PAGE and immunoblotting with anti-HA antibody.
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References

    1. Taylor SS, Kim C, Vigil D, Haste NM, Yang J, Wu J, et al. Dynamics of signaling by PKA. Biochim Biophys Acta. 2005;1754:25–37. - PubMed
    1. Walsh DA, Perkins JP, Krebs EG. An adenosine 3′,5′-monophosphate-dependant protein kinase from rabbit skeletal muscle. J Biol Chem. 1968;243:3763–3765. - PubMed
    1. Rubio-Texeira M, Van Zeebroeck G, Voordeckers K, Thevelein JM. Saccharomyces cerevisiae plasma membrane nutrient sensors and their role in PKA signaling. FEMS Yeast Res. 2009;10:134–149. - PubMed
    1. Xue Y, Batlle M, Hirsch JP. GPR1 encodes a putative G protein-coupled receptor that associates with the Gpa2p Gα subunit and functions in a Ras-independent pathway. EMBO J. 1998;17:1996–2007. - PMC - PubMed
    1. Kraakman L, Lemaire K, Ma P, Teunissen AWRH, Donaton MCV, Van Dijck P, et al. A Saccharomyces cerevisiae G-protein coupled receptor, Gpr1, is specifically required for glucose activation of the cAMP pathway during the transition to growth on glucose. Mol Microbiol. 1999;32:1002–1012. - PubMed

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