An activating mutation in the γ1 subunit of the AMP‐activated protein kinase

By S. Hamilton, D. Stapleton, J. B. O'Donnell, J. Kung, S. Dalal, Bruce E. Kemp, L. Witters. 2001

98 citations recorded by the source corpus.

The AMP‐activated protein kinase (AMPK) is a heterotrimeric protein composed of a catalytic α subunit and two regulatory subunits, β and γ. The γ subunit is essential for enzyme activity by virtue of its binding to the C‐terminus of the α subunit and appears to play some role in the determination of AMP sensitivity. We demonstrate that a γ1R70Q mutation causes a marked increase in AMPK activity and renders it largely AMP‐independent. This activation is associated with increased phosphorylation of the α subunit activation loop T172. These in vitro characteristics of AMPK are also reflected in increased intracellular phosphorylation of one of its major substrates, acetyl‐CoA carboxylase. These data illustrate the importance of the γ1 subunit in the regulation of AMPK and its modulation by AMP.

Subfields: Molecular Biology, Physiology, Surgery

View Paper: https://www.semanticscholar.org/paper/4e6865bdb3280435f35238397b3e37085c31a0e4

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. D. Hardie
2. David Carling
3. S. Hawley
4. Bruce E. Kemp
5. David M. Sabatini
6. J. Scott
7. K. Green
8. B. Kahn

In Physiology

1. D. Hardie
2. David Carling
3. Bruce E. Kemp
4. S. Hawley
5. B. Kahn
6. B. Manning
7. W. Kaelin
8. L. Ellisen

In Surgery

1. D. Hardie
2. David Carling
3. S. Hawley
4. Bruce E. Kemp
5. K. Green
6. J. Scott
7. B. Kahn
8. T. Alquier

Citations in the corpus

• Intrasteric control of AMPK via the γ1 subunit AMP allosteric regulatory site (2004, methodology): “A 1 mutation, R70Q, in the first CBS domain, causes a loss of AMP dependence (Hamilton et al. 2001).”
• AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. (2005, background): “The equivalent mutation in γ1 (R70Q) has not yet been found to occur naturally but appears to be more active than the wildtype under basal conditions when expressed in cultured cells (Hamilton et al., 2001).”
• CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations. (2004, background): “Neither our results nor those of Daniel and Carling (37) support two previous claims (12, 36) that WPWS mutations make AMPK complexes constitutively active.”
• Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. (2004, methodology): “AMPK kinase assays were as described with minor modifications (Hamilton et al. 2001).”