Regulation of polypeptide‐chain initiation in rat skeletal muscle Starvation does not alter the activity or phosphorylation state of initiation factor eIF‐2

Cox, Sarah; Redpath, Nicholas T.; Proud, Christopher G.

doi:10.1016/0014-5793(88)80946-3

Cited by 22 publications

(4 citation statements)

References 30 publications

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“…In these experiments insulin did not affect the level of eIF2a phosphorylation as assessed by isoelectric focusing ( = 15% with or without insulin; data not shown). This observation is consistent with other work in muscle [11,13,32,33] and in Swiss 3T3 cells [14] showing that insulin or diabetes do not affect the state of phosphorylation of eIF2a and points to an alternative mechanism regulating the activity of eIF2B.…”

Section: Insulin Activates Eif2b and Inactivates Gsk-3 In Choirsupporting

confidence: 93%

Activation of translation initiation factor eIF2B by insulin requires phosphatidyl inositol 3‐kinase

et al. 1997

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Eukaryotic initiation factor eIF2B mediates a key regulatory step in peptide-chain initiation and is acutely activated by insulin, although it is not clear how. Inhibitors of phosphatidylinositide 3-kinase blocked activation of eIF2B, although rapamycin, which inhibits the p70 S6 kinase pathway, did not. Furthermore, a dominant negative mutant of PI 3-kinase also prevented activation of eIF2B, while a Sos-mutant, which blocks MAP kinase activation, did not. The data demonstrate that a pathway distinct from MAP and p70 S6 kinases regulates eIF2B. Glycogen synthase kinase-3 (GSK-3) phosphorylates and inactivates eIF2B. In all cases, eIF2B and GSK-3 were regulated reciprocally. Dominant negative PI 3-kinase abolished the insulin-induced inhibition of GSK-3. These data strongly support the hypothesis that insulin activates eIF2B through a signalling pathway involving PI 3-kinase and inhibition of GSK-3.

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Section: Insulin Activates Eif2b and Inactivates Gsk-3 In Choirsupporting

confidence: 93%

Activation of translation initiation factor eIF2B by insulin requires phosphatidyl inositol 3‐kinase

et al. 1997

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“…Previous studies have shown that neither the activity of eIF2B nor the phosphorylation of eIF2␣ in mature rats changes with feeding (4,55). However, we hypothesized that the initiation factors involved in the formation of the 43S preinitation complex might be activated by feeding in immature animals, because the stimulation of muscle protein synthesis by feeding is markedly elevated in the neonate (5,7,9).…”

Section: Discussionmentioning

confidence: 88%

Developmental changes in the feeding-induced stimulation of translation initiation in muscle of neonatal pigs

Davis

Nguyen

Suryawan

et al. 2000

American Journal of Physiology-Endocrinology and Metabolism

153

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The rapid gain in skeletal muscle mass in the neonate is associated with a marked elevation in skeletal muscle protein synthesis in response to feeding. The feeding-induced response decreases with development. To determine whether the response to feeding is regulated at the level of translation initiation, the expression, phosphorylation, and function of a number of eukaryotic initiation factors (eIF) were examined. Pigs at 7 and 26 days of age were either fasted overnight or fed porcine milk after an overnight fast. In muscle of 7-day-old pigs, the hyperphosphorylated form of the eIF4E repressor protein, 4E-binding protein 1 (4E-BP1), was undetectable in the fasting state but rose to 60% of total 4E-BP1 after feeding; eIF4E phosphorylation was unaffected by feeding status. The amount of eIF4E in the inactive 4E-BP1. eIF4E complex was reduced by 80%, and the amount of eIF4E in the active eIF4E. eIF4G complex was increased 14-fold in muscle of 7-day-old pigs after feeding. The amount of 70-kDa ribosomal protein S6 (p70(S6)) kinase in the hyperphosphorylated form rose 2.5-fold in muscle of 7-day-old pigs after feeding. Each of these feeding-induced responses was blunted in muscle of 26-day-old pigs. eIF2B activity in muscle was unaffected by feeding status but decreased with development. Feeding produced similar changes in eIF characteristics in liver and muscle; however, the developmental changes in liver were not as apparent as in skeletal muscle. Thus the results demonstrate that the developmental change in the acute stimulation of skeletal muscle protein synthesis by feeding is regulated by the availability of eIF4E for 48S ribosomal complex formation. The results further suggest that the overall developmental decline in skeletal muscle protein synthesis involves regulation by eIF2B.

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“…These phenomena occur without a detectable change in eIF2B activity (37). Moreover, 48-h starvation is without effect on the activity of eIF2B although protein synthesis diminishes (1). Thus, although protein synthesis is regulated by eIF2B under a variety of circumstances (8), particular nutritional states and glucocorticoid treatment share a mode of regulation mediated by eIF4F and independent of eIF2B.…”

Section: Discussionmentioning

confidence: 98%

Acute attenuation of translation initiation and protein synthesis by glucocorticoids in skeletal muscle

Shah

Kimball

Jefferson

2000

American Journal of Physiology-Endocrinology and Metabolism

112

100

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Glucocorticoids are diabetogenic factors that not only antagonize the action of insulin in target tissues but also render these tissues catabolic. Therefore, in rats, we endeavored to characterize the effects in skeletal muscle of glucocorticoids on translation initiation, a regulated process that, in part, governs overall protein synthesis through the modulated activities of eukaryotic initiation factors (eIFs). Four hours after intraperitoneal administration of dexamethasone (100 microg/100 g body wt), protein synthesis in skeletal muscle was reduced to 59% of the value recorded in untreated control animals. Furthermore, translation initiation factor eIF4E preferred association with its endogenous inhibitor 4E-BP1 rather than eIF4G. Dexamethasone treatment resulted in dephosphorylation of both 4E-BP1 and the 40S ribosomal protein S6 kinase concomitant with enhanced phosphorylation of eIF4E. Moreover, the guanine nucleotide exchange activity of eIF2B was unaffected as was phosphorylation of the alpha-subunit of eIF2. Hence glucocorticoids negatively modulate the activation of a subset of the protein synthetic machinery, thereby contributing to the catabolic properties of this class of hormones in vivo.

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Regulation of polypeptide‐chain initiation in rat skeletal muscle Starvation does not alter the activity or phosphorylation state of initiation factor eIF‐2

Cited by 22 publications

References 30 publications

Activation of translation initiation factor eIF2B by insulin requires phosphatidyl inositol 3‐kinase

Activation of translation initiation factor eIF2B by insulin requires phosphatidyl inositol 3‐kinase

Developmental changes in the feeding-induced stimulation of translation initiation in muscle of neonatal pigs

Acute attenuation of translation initiation and protein synthesis by glucocorticoids in skeletal muscle

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