Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.31 (AMP-activated protein kinase)
 13,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Muscle contractions activate protein kinases, leading to signal transduction. We hypothesized that kinase activation would be influenced by mitochondrial content, as well as by contractile activity-induced increases in muscle O(2) consumption (Vo(2)). Kinase phosphorylation in high-oxidative red and low-oxidative white tibialis anterior (TA) muscle (RTA and WTA, respectively) with 2.5-fold differences in mitochondrial content were compared. Stimulation of the TA muscle elicited large increases in Vo(2) (3- to 6-fold and 4- to 60-fold above resting levels in WTA and RTA, respectively). At rest, AMP-activated protein kinase (AMPK), p38, p42, and p44 activation were nearly twofold greater in WTA than in RTA, suggesting an inverse relationship between mitochondrial content and kinase activation in resting muscle. During contractions, similar degrees of phosphorylation in RTA and WTA were evident as a function of Vo(2) for p38 and p42. During increases in Vo(2) up to sixfold above rest, greater responses were observed in RTA than in WTA for AMPK and p44, whereas Akt activation was greater in WTA. In RTA, elevations in Vo(2) elicited increases in AMPK and p44 activation, whereas Akt, p38, and p42 were less sensitive to increments in Vo(2). Reactive oxygen species (ROS) production was greater in mitochondria from white muscle, but when it was calculated in the context of the whole muscle, ROS production was twofold greater in red than in white myofibers. Thus mitochondrial content influences ROS production and is inversely related to kinase activation in resting muscle. During contractions, kinases are differentially sensitive to contraction-induced increments in Vo(2), suggesting that muscle mitochondrial content is important, but it is not the sole determinant of kinase activation during exercise of different intensities.
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PMID:Kinase-specific responsiveness to incremental contractile activity in skeletal muscle with low and high mitochondrial content. 1849 78

The vacuolar H(+)-ATPase (V-ATPase) mediates ATP-driven H(+) transport across membranes. This pump is present at the apical membrane of kidney proximal tubule cells and intercalated cells. Defects in the V-ATPase and in proximal tubule function can cause renal tubular acidosis. We examined the role of protein kinase A (PKA) and AMP-activated protein kinase (AMPK) in the regulation of the V-ATPase in the proximal tubule as these two kinases coregulate the V-ATPase in the collecting duct. As the proximal tubule V-ATPases have different subunit compositions from other nephron segments, we postulated that V-ATPase regulation in the proximal tubule could differ from other kidney tubule segments. Immunofluorescence labeling of rat ex vivo kidney slices revealed that the V-ATPase was present in the proximal tubule both at the apical pole, colocalizing with the brush-border marker wheat germ agglutinin, and in the cytosol when slices were incubated in buffer alone. When slices were incubated with a cAMP analog and a phosphodiesterase inhibitor, the V-ATPase accumulated at the apical pole of S3 segment cells. These PKA activators also increased V-ATPase apical membrane expression as well as the rate of V-ATPase-dependent extracellular acidification in S3 cell monolayers relative to untreated cells. However, the AMPK activator AICAR decreased PKA-induced V-ATPase apical accumulation in proximal tubules of kidney slices and decreased V-ATPase activity in S3 cell monolayers. Our results suggest that in proximal tubule the V-ATPase subcellular localization and activity are acutely coregulated via PKA downstream of hormonal signals and via AMPK downstream of metabolic stress.
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PMID:Regulation of proximal tubule vacuolar H(+)-ATPase by PKA and AMP-activated protein kinase. 2455 31