scholarly journals Ca2+/Calmodulin-Dependent Protein Kinase Kinase-  Regulates Skeletal Muscle Glucose Uptake Independent of AMP-Activated Protein Kinase and Akt Activation

Diabetes ◽  
2007 ◽  
Vol 56 (5) ◽  
pp. 1403-1409 ◽  
Author(s):  
C. A. Witczak ◽  
N. Fujii ◽  
M. F. Hirshman ◽  
L. J. Goodyear
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Glucose Uptake ◽  
Dependent Protein Kinase ◽  
Akt Activation ◽  
Dependent Protein ◽  
Skeletal Muscle Glucose Uptake ◽  
Amp Activated Protein Kinase ◽  
Protein Kinase Kinase

Skeletal Muscle Glucose Uptake During Exercise: How is it Regulated?

Physiology ◽  
2005 ◽  
Vol 20 (4) ◽  
pp. 260-270 ◽  
Author(s):  
Adam J. Rose ◽  
Erik A. Richter
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Glucose Uptake ◽  
Intracellular Signaling ◽  
Surface Membrane ◽  
Capillary Perfusion ◽  
Subsequent Increase ◽  
Dependent Protein ◽  
Skeletal Muscle Glucose Uptake ◽  
Amp Activated Protein Kinase

The increase in skeletal muscle glucose uptake during exercise results from a coordinated increase in rates of glucose delivery (higher capillary perfusion), surface membrane glucose transport, and intracellular substrate flux through glycolysis. The mechanism behind the movement of GLUT4 to surface membranes and the subsequent increase in transport by muscle contractions is largely unresolved, but it is likely to occur through intracellular signaling involving Ca2+-calmodulin-dependent protein kinase, 5′-AMP-activated protein kinase, and possibly protein kinase C.

scholarly journals Binding and structural analyses of potent inhibitors of the human Ca2+/calmodulin dependent protein kinase kinase 2 (CAMKK2) identified from a collection of commercially-available kinase inhibitors

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Gerson S. Profeta ◽  
Caio V. dos Reis ◽  
André da S. Santiago ◽  
Paulo H. C. Godoi ◽  
Angela M. Fala ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Small Molecule ◽  
Kinase Inhibitors ◽  
Titration Calorimetry ◽  
Dependent Protein Kinase ◽  
Regulatory Pathways ◽  
Calcium Calmodulin Dependent ◽  
Dependent Protein ◽  
Amp Activated Protein Kinase ◽  
Protein Kinase Kinase

Abstract Calcium/Calmodulin-dependent Protein Kinase Kinase 2 (CAMKK2) acts as a signaling hub, receiving signals from various regulatory pathways and decoding them via phosphorylation of downstream protein kinases - such as AMPK (AMP-activated protein kinase) and CAMK types I and IV. CAMKK2 relevance is highlighted by its constitutive activity being implicated in several human pathologies. However, at present, there are no selective small-molecule inhibitors available for this protein kinase. Moreover, CAMKK2 and its closest human homolog, CAMKK1, are thought to have overlapping biological roles. Here we present six new co-structures of potent ligands bound to CAMKK2 identified from a library of commercially-available kinase inhibitors. Enzyme assays confirmed that most of these compounds are equipotent inhibitors of both human CAMKKs and isothermal titration calorimetry (ITC) revealed that binding to some of these molecules to CAMKK2 is enthalpy driven. We expect our results to advance current efforts to discover small molecule kinase inhibitors selective to each human CAMKK.

scholarly journals Differential AMP-activated Protein Kinase (AMPK) Recognition Mechanism of Ca2+/Calmodulin-dependent Protein Kinase Kinase Isoforms

2016 ◽  
Vol 291 (26) ◽  
pp. 13802-13808 ◽  
Author(s):  
Yuya Fujiwara ◽  
Yoshinori Kawaguchi ◽  
Tomohito Fujimoto ◽  
Naoki Kanayama ◽  
Masaki Magari ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Dependent Protein Kinase ◽  
Recognition Mechanism ◽  
Dependent Protein ◽  
Amp Activated Protein Kinase ◽  
Protein Kinase Kinase

scholarly journals Calmodulin-dependent protein kinase kinase-β is an alternative upstream kinase for AMP-activated protein kinase

2005 ◽  
Vol 2 (1) ◽  
pp. 9-19 ◽  
Author(s):  
Simon A. Hawley ◽  
David A. Pan ◽  
Kirsty J. Mustard ◽  
Louise Ross ◽  
Jenny Bain ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Dependent Protein Kinase ◽  
Upstream Kinase ◽  
Dependent Protein ◽  
Amp Activated Protein Kinase ◽  
Protein Kinase Kinase

Ca2+/calmodulin-dependent protein kinase kinase is involved in AMP-activated protein kinase activation by α-lipoic acid in C2C12 myotubes

2007 ◽  
Vol 293 (4) ◽  
pp. C1395-C1403 ◽  
Author(s):  
Qingwu W. Shen ◽  
Mei J. Zhu ◽  
Junfeng Tong ◽  
Jun Ren ◽  
Min Du
Keyword(s):  
Protein Kinase ◽  
Lipoic Acid ◽  
Fluorescent Microscopy ◽  
C2c12 Myotubes ◽  
Ampk Activation ◽  
Dependent Protein Kinase ◽  
Α Subunit ◽  
Dependent Protein ◽  
Amp Activated Protein Kinase ◽  
Protein Kinase Kinase

-α-Lipoic acid (ALA) widely exists in foods and is an antidiabetic agent. ALA stimulates glucose uptake and increases insulin sensitivity by the activation of AMP-activated protein kinase (AMPK) in skeletal muscle, but the underlying mechanism for AMPK activation is unknown. Here, we investigated the mechanism through which ALA activates AMPK in C2C12 myotubes. Incubation of C2C12 myotubes with 200 and 500 μM ALA increased the activity and phosphorylation of the AMPK α-subunit at Thr172. Phosphorylation of the AMPK substrate, acetyl CoA carboxylase (ACC), at Ser79 was also increased. No difference in ATP, AMP, and the calculated AMP-to-ATP ratio was observed among the different treatment groups. Since the upstream AMPK kinase, LKB1, requires an alteration of the AMP-to-ATP ratio to activate AMPK, this data showed that LKB1 might not be involved in the activation of AMPK induced by ALA. Treatment of ALA increased the intracellular Ca2+ concentration measured by fura-2 fluorescent microscopy ( P < 0.05), showing that ALA may activate AMPK through enhancing Ca2+/calmodulin-dependent protein kinase kinase (CaMKK) signaling. Indeed, chelation of intracellular free Ca2+ by loading cells with 25 μM BAPTA-AM for 30 min abolished the ALA-induced activation of AMPK and, in turn, phosphorylation of ACC at Ser79. Furthermore, inhibition of CaMKK using its selective inhibitor, STO-609, abolished ALA-stimulated AMPK activation, with an accompanied reduction of ACC phosphorylation at Ser79. In addition, ALA treatment increased the association of AMPK with CaMKK. To further show the role of CaMKK in AMPK activation, short interfering RNA was used to silence CaMKK, which abolished the ALA-induced AMPK activation. These data show that CaMKK is the kinase responsible for ALA-induced AMPK activation in C2C12 myotubes.

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