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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #198648
Title: DEVELOPMENTAL REGULATION OF PROTEIN KINASE B ACTIVATION IS ISOFORM SPECIFIC IN SKELETAL MUSCLE OF NEONATAL PIGS

Author
item Suryawan, Agus
item Davis, Teresa

Submitted to: Pediatric Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/14/2005
Publication Date: 10/1/2005
Citation: Suryawan, A., Davis, T.A. 2005. Developmental regulation of protein kinase B activation is isoform specific in skeletal muscle of neonatal pigs. Pediatric Research. 58(4):719-724.

Interpretive Summary: After consuming food, insulin signaling components that lead to the stimulation of muscle protein biosynthesis are activated. Due to higher growth rate of newborn animals, the activation of this insulin signal is higher in newborns and decreases with development. Protein kinase B (PKB), one of the major insulin signaling components, has three families: PKBalpha, PKBbeta, and PKBgamma. The amount of PKBbeta and PKBgamma protein is higher in newborn pigs (7-day) than in older pigs (26-day). The activation of 3'-phosphoinositide-dependent kinase-1 (PDK-1), a protein that helps to activate PKB, is also higher in newborn pigs compared to older pigs. In conclusion, the higher activation of PKB and PDK-1 is consistent with the higher activation insulin signaling pathway in skeletal muscle of newborn animals.

Technical Abstract: 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.