AMPK β subunits display isoform specific affinities for carbohydrates

Koay, Ann; Woodcroft, Ben J.; Petrie, Emma J.; Yue, Helen; Emanuelle, Shane; Bieri, Martin; Bailey, Michael F.; Hargreaves, Mark; Park, Jong-Tae; Park, Kwan-Hwa; Ralph, Stuart A.; Neumann, Dietbert; Stapleton, David; Gooley, Paul R.

doi:10.1016/j.febslet.2010.07.015

Cited by 61 publications

(76 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Such recognition of helical glucan conformation has been reported for a bacterial glucan binding protein (Koropatkin et al, 2008). The CBM48 domain of the b-subunit of AMP kinase also appears to have higher affinity for cyclodextrin over maltoheptaose in some NMR studies (Koay et al, 2010), although not in others (Koay et al, 2007).…”

Section: Ptst2 May Determine the Glucan Substrates Available To Ss4mentioning

confidence: 55%

Homologs of PROTEIN TARGETING TO STARCH Control Starch Granule Initiation in Arabidopsis Leaves

et al. 2017

View full text Add to dashboard Cite

ORCID IDs: 0000-0003-3905-3647 (D.S.); 0000-0002-8569-9150 (J.B.); 0000-0001-8682-5668 (J.M.); 0000-0002-4440-1776 (T.B.S.); 0000-0002-9501-7854 (M.Z.); 0000-0002-2791-0915 (S.C.Z.)The molecular mechanism that initiates the synthesis of starch granules is poorly understood. Here, we discovered two plastidial proteins involved in granule initiation in Arabidopsis thaliana leaves. Both contain coiled coils and a family-48 carbohydrate binding module (CBM48) and are homologs of the PROTEIN TARGETING TO STARCH (PTST) protein; thus, we named them PTST2 and PTST3. Chloroplasts in mesophyll cells typically contain five to seven granules, but remarkably, most chloroplasts in ptst2 mutants contained zero or one large granule. Chloroplasts in ptst3 had a slight reduction in granule number compared with the wild type, while those of the ptst2 ptst3 double mutant contained even fewer granules than ptst2. The ptst2 granules were larger but similar in morphology to wild-type granules, but those of the double mutant had an aberrant morphology. Immunoprecipitation showed that PTST2 interacts with STARCH SYNTHASE4 (SS4), which influences granule initiation and morphology. Overexpression of PTST2 resulted in chloroplasts containing many small granules, an effect that was dependent on the presence of SS4. Furthermore, isothermal titration calorimetry revealed that the CBM48 domain of PTST2, which is essential for its function, interacts with long maltooligosaccharides. We propose that PTST2 and PTST3 are critical during granule initiation, as they bind and deliver suitable maltooligosaccharide primers to SS4.

show abstract

Section: Ptst2 May Determine the Glucan Substrates Available To Ss4mentioning

confidence: 55%

Homologs of PROTEIN TARGETING TO STARCH Control Starch Granule Initiation in Arabidopsis Leaves

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Both isoforms are 71% identical and differ mostly at the N-terminal region (Thornton et al, 1998). Additionally, there have been studies showing that the carbohydrate-binding module (CBM) of the b2 subunit binds more tightly to oligosaccharides when compared with the b1 subunit (Koay et al, 2010). One of the main reasons for this was shown to be a single threonine insertion at position 101 in AMPKb2 after Trp99 (Koay et al, 2010).…”

Section: General Introductionmentioning

confidence: 99%

“…Additionally, there have been studies showing that the carbohydrate-binding module (CBM) of the b2 subunit binds more tightly to oligosaccharides when compared with the b1 subunit (Koay et al, 2010). One of the main reasons for this was shown to be a single threonine insertion at position 101 in AMPKb2 after Trp99 (Koay et al, 2010). The latter residue has been shown to be essential for oligosaccharide binding and glycogen association in vitro (Polekhina et al, 2005;McBride et al, 2009), and insertion of Thr101 in the CBM region of the b1 subunit resulted in an increased affinity for oligosaccharides (Koay et al, 2010).…”

Section: General Introductionmentioning

confidence: 99%

Adenosine Monophosphate–Activated Kinase and Its Key Role in Catabolism: Structure, Regulation, Biological Activity, and Pharmacological Activation

2014

View full text Add to dashboard Cite

Adenosine monophosphate-activated protein kinase (AMPK) is a cellular energy sensor, which once activated, plays a role in several processes within the cell to restore energy homeostasis. The protein enhances catabolic pathways, such as b-oxidation and autophagy, to generate ATP, and inhibits anabolic processes that require energy, including fatty acid, cholesterol, and protein synthesis. Due to its key role in the regulation of critical cellular pathways, deregulation of AMPK is associated with the pathology of many diseases, including cancer, Wolff-Parkinson-White syndrome, neurodegenerative disorders, diabetes, and metabolic syndrome. In fact, AMPK is a target of some pharmacological agents implemented in the treatment of diabetes (metformin and thiazolidinediones) as well as other naturally derived products, such as berberine, which is used in traditional medicine. Due to its critical role in the cell and the pathology of several disorders, research into developing AMPK as a therapeutic target is becoming a burgeoning and exciting field of pharmacological research. A profound understanding of the regulation and activity of AMPK would enhance its development as a promising therapeutic target.

show abstract

“…In the present study, we show that R6 preferentially interacts with AMPKβ2, rather than AMPKβ1, pointing to a possible role for this interaction in skeletal muscle. The CBM domain of AMPKβ2 possesses higher binding affinity for carbohydrates such as glycogen than β1 (14). In a more detailed study the CBM domain of AMPKβ2 bound linear carbohydrates and single α1,6-branched carbohydrates 4-30 fold tighter in comparison with β1 (36).…”

Section: Discussionmentioning

confidence: 99%

The interaction between AMPKβ2 and the PP1-targeting subunit R6 is dynamically regulated by intracellular glycogen content

Oligschlaeger

Miglianico

Dahlmans

et al. 2016

Biochemical Journal

Self Cite

View full text Add to dashboard Cite

AMP-activated protein kinase (AMPK) is a metabolic stress-sensing kinase. We previously showed that glucose deprivation induces autophosphorylation of AMPKβ at threonine-148 (Thr-148), which prevents the binding of AMPK to glycogen. Furthermore, in MIN6 cells, AMPKβ1 binds to R6 (PPP1R3D), a glycogen-targeting subunit of protein phosphatase 1 (PP1), thereby regulating the glucose-induced inactivation of AMPK. Here, we further investigated the interaction of R6 with AMPKβ and the possible dependency on Thr-148 phosphorylation status. Yeast two-hybrid analyses and co-immunoprecipitation of the overexpressed proteins in HEK293T cells revealed that both AMPKβ1 and β2 wild-type (WT) isoforms bind to R6. The AMPKβ/R6 interaction was stronger with the muscle-specific β2-WT and required association with the substrate-binding motif of R6. When HEK293T cells or C2C12 myotubes were cultured in high-glucose medium, AMPKβ2-WT and R6 weakly interacted. In contrast, glycogen depletion significantly enhanced this protein interaction. Mutation of AMPKβ2 Thr-148 prevented the interaction with R6 irrespective of the intracellular glycogen content. Treatment with the AMPK activator oligomycin enhanced AMPKβ2/R6 interaction in conjunction with increased Thr-148 phosphorylation in cells grown in low glucose medium. These data are in accordance with R6 binding directly to AMPKβ2 when both proteins detach from the diminishing glycogen particle, which is simultaneous to increased AMPKβ2 Thr-148 autophosphorylation. Such model points to a possible control of AMPK by PP1-R6 upon glycogen depletion in muscle. SUMMARY STATEMENTBreakdown of intracellular glycogen enhances interaction of the AMPKβ2 subunit and the R6 glycogentargeting subunit of the protein phosphatase-1 (PP1), which occurs in conjunction with increased β2-threonine-148 phosphorylation. SHORT TITLEGlycogen-dependent regulation of AMPKβ2/R6 interaction

show abstract

AMPK β subunits display isoform specific affinities for carbohydrates

Cited by 61 publications

References 24 publications

Homologs of PROTEIN TARGETING TO STARCH Control Starch Granule Initiation in Arabidopsis Leaves

Homologs of PROTEIN TARGETING TO STARCH Control Starch Granule Initiation in Arabidopsis Leaves

Adenosine Monophosphate–Activated Kinase and Its Key Role in Catabolism: Structure, Regulation, Biological Activity, and Pharmacological Activation

The interaction between AMPKβ2 and the PP1-targeting subunit R6 is dynamically regulated by intracellular glycogen content

Contact Info

Product

Resources

About