Developmental regulation of protein kinase B activation is isoform specific in skeletal muscle of neonatal pigs.
The postprandial activation of the insulin signaling pathway that leads to translation initiation is enhanced in skeletal muscle of the neonate and decreases with development in parallel with the developmental decline in muscle protein synthesis. Our previous study showed that the activity of protein kinase B (PKB), a major insulin signaling component, was higher in 7- than in 26-d-old pigs. To examine the molecular mechanisms involved, we determined PKB isoform abundance and phosphorylation state, the abundance of its kinases, and PKB's association with its kinases. The abundances of total PKB, PKBalpha, and PKBgamma were higher in muscle of 7- than in 26-d-old pigs whereas PKBbeta abundance was similar in the two age groups. PKB phosphorylation at Thr308 was higher in 7- than in 26-d-old pigs but PKB phosphorylation at Ser473 was similar in both age groups. The association of PKB with 3'-phosphoinositide-dependent kinase-1 (PDK-1), a kinase that phosphorylates PKB at Thr308, and PDK-1 abundance were higher in 7- than in 26-d-old pigs. Moreover, PDK-1 phosphorylation at Ser-241, a site that is crucial for PDK-1 activation, was higher in 7- than in 26-d-old pigs. However, the association of PKB with integrin-linked kinase (ILK), a kinase that potentially phosphorylates PKB at Ser473, and ILK abundance were similar in both age groups. The result suggests that the developmental change in PKB activation is isoform specific and involves regulation by PDK-1.
Suryawan
Agus
A
USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
Davis
Teresa A
TA
D064413:3-Phosphoinositide-Dependent Protein Kinases; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D047468:Immunoprecipitation; D007328:Insulin / Q000378:metabolism; D018482:Muscle, Skeletal / Q000196:embryology* / Q000201:enzymology / Q000378:metabolism; D010766:Phosphorylation; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000737:chemistry* / Q000378:metabolism*; D012694:Serine / Q000737:chemistry; D015398:Signal Transduction; D013552:Swine; D013912:Threonine / Q000737:chemistry; D013997:Time Factors; D000099200:Scaffold Protein ILK
D064413:3-Phosphoinositide-Dependent Protein Kinases; D007328:Insulin; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D012694:Serine; D013912:Threonine; D000099200:Scaffold Protein ILK