Research Topics
Genomes and Genes
| L S JeffersonSummaryAffiliation: Pennsylvania State University Country: USA Publications
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Publications
Glycogen synthase kinase-3 is the predominant insulin-regulated eukaryotic initiation factor 2B kinase in skeletal muscleL S Jefferson
Department of Cellular and Molecular Physiology, Pennsylvania State University, College of Medicine, Hershey 17033, USA
Int J Biochem Cell Biol 31:191-200. 1999..Thus, insulin-mediated changes in eIF2B activity are likely to involve GSK-3...
Amino acid regulation of gene expressionL S Jefferson
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
J Nutr 131:2460S-6S; discussion 2486S-7S. 2001..It concludes with a consideration of some of the important unanswered questions in this rapidly advancing area of research...
Amino acids as regulators of gene expression at the level of mRNA translationLeonard S Jefferson
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
J Nutr 133:2046S-2051S. 2003..Finally, it provides examples of mRNAs whose translation is modulated through these mechanisms...
Signaling pathways and molecular mechanisms through which branched-chain amino acids mediate translational control of protein synthesisScot R Kimball
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA, USA
J Nutr 136:227S-31S. 2006..The current state of our understanding of how leucine acts on these signaling pathways and molecular mechanisms to stimulate protein synthesis in skeletal muscle is summarized in this article...
Time course changes in signaling pathways and protein synthesis in C2C12 myotubes following AMPK activation by AICARDavid L Williamson
Dept of Cellular and Molecular Physiology, H166, Pennsylvania State University College of Medicine, 500 University Dr, Hershey, PA 17033, USA
Am J Physiol Endocrinol Metab 291:E80-9. 2006....
Identification of domains within the epsilon-subunit of the translation initiation factor eIF2B that are necessary for guanine nucleotide exchange activity and eIF2B holoprotein formationT G Anthony
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA
Biochim Biophys Acta 1492:56-62. 2000..In contrast, the C-terminal domain of eIF2B epsilon is sufficient alone for binding the beta-subunit of its substrate, eIF2, in vitro...
Chronic alcohol feeding impairs hepatic translation initiation by modulating eIF2 and eIF4EC H Lang
Department of Cellular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
Am J Physiol 277:E805-14. 1999..In summary, these data suggest that chronic alcohol consumption impairs translation initiation in liver by altering eIF2B activity as well as eIF4F function via changes in eIF4E availability...
Inhibition of muscle protein synthesis by alcohol is associated with modulation of eIF2B and eIF4EC H Lang
Departments of Cellular and Molecular Physiology and Surgery, Pennsylvania State College of Medicine, Hershey, Pennsylvania 17033, USA
Am J Physiol 277:E268-76. 1999..In summary, these data suggest that chronic alcohol consumption impairs translation initiation in muscle by altering multiple regulatory sites, including eIF2B activity and eIF4E availability...
Feeding stimulates protein synthesis in muscle and liver of neonatal pigs through an mTOR-dependent processS R Kimball
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
Am J Physiol Endocrinol Metab 279:E1080-7. 2000..However, in skeletal muscle, these two processes may account for only part of the stimulation of protein synthesis, and thus additional steps may be involved in the response...
Regulation of amino acid-sensitive TOR signaling by leucine analogues in adipocytesC J Lynch
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
J Cell Biochem 77:234-51. 2000....
Regulation of protein synthesis after acute resistance exercise in diabetic ratsP A Farrell
Noll Physiological Research Center and Department of Kinesiology, University Park 16802 and Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
Am J Physiol 276:E721-7. 1999..This preserved response may be due to a compensatory increase in muscle IGF-I content and a maintained ability to activate eIF2B...
Amino acid-induced stimulation of translation initiation in rat skeletal muscleT C Vary
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
Am J Physiol 277:E1077-86. 1999..eIF4G complex controls protein synthesis in skeletal muscle when the amino acid concentration is above the physiological range, whereas removal of leucine reduces protein synthesis through changes in both eIF2B and eIF4E...
Deficiency of dietary EAA preferentially inhibits mRNA translation of ribosomal proteins in liver of meal-fed ratsT G Anthony
Department of Cellular and Molecular Physiology, Pennsylvania State College of Medicine, Hershey, PA 17033, USA
Am J Physiol Endocrinol Metab 281:E430-9. 2001..Additionally, the translation of rp mRNAs is preferentially repressed in association with decreased S6K1 phosphorylation...
Oral administration of leucine stimulates ribosomal protein mRNA translation but not global rates of protein synthesis in the liver of ratsT G Anthony
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
J Nutr 131:1171-6. 2001..Furthermore, the translation of rp mRNA is disjointed from rates of total protein synthesis in liver and related to the degree of S6K1 phosphorylation...
Initiation of protein synthesis in a cell-free system prepared from rat hepatocytesS R Kimball
Department of Physiology, College of Medicine, Pennsylvania State University, Hershey 17033
Am J Physiol 256:C28-34. 1989..The cell-free system should provide a valuable tool for investigation of mechanisms involved in the regulation of initiation of protein synthesis...
Role of eIF4E in stimulation of protein synthesis by IGF-I in perfused rat skeletal muscleT C Vary
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
Am J Physiol Endocrinol Metab 278:E58-64. 2000..In contrast, the amount of eIF4E bound to eIF4G was increased threefold by IGF-I. We conclude that IGF-I regulates protein synthesis in skeletal muscle by enhancing formation of the active eIF4E x eIF4G complex...
Regulation of guanine nucleotide exchange through phosphorylation of eukaryotic initiation factor eIF2alpha. Role of the alpha- and delta-subunits of eiF2bS R Kimball
Department of Cellular and Molecular Physiology, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033, USA
J Biol Chem 273:12841-5. 1998..The results provide the first direct biochemical evidence that the alpha- and delta-subunits of eIF2B are involved in mediating the effect of substrate phosphorylation...
Implication of eIF2B rather than eIF4E in the regulation of global protein synthesis by amino acids in L6 myoblastsS R Kimball
Department of Cellular and Molecular Physiology, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033, USA
J Biol Chem 273:30945-53. 1998..Furthermore, under the conditions employed herein, alterations in eIF4E availability are not rate-controlling for global protein synthesis but might be necessary for regulation of translation of specific mRNAs...
Identification of interprotein interactions between the subunits of eukaryotic initiation factors eIF2 and eIF2BS R Kimball
Department of Cellular and Molecular Physiology, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033, USA
J Biol Chem 273:3039-44. 1998....
Insulin fails to stimulate muscle protein synthesis in sepsis despite unimpaired signaling to 4E-BP1 and S6K1T C Vary
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 10733, USA
Am J Physiol Endocrinol Metab 281:E1045-53. 2001..Thus the inability of insulin to stimulate protein synthesis during sepsis may be related to a defect in signaling to a step in translation initiation involved in assembly of an active eIF4F complex...
Mechanism of inhibition of peptide chain initiation by amino acid deprivation in perfused rat liver. Regulation involving inhibition of eukaryotic initiation factor 2 alpha phosphatase activityS R Kimball
Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey 17033
J Biol Chem 266:1969-76. 1991....
Leucine regulates translation of specific mRNAs in L6 myoblasts through mTOR-mediated changes in availability of eIF4E and phosphorylation of ribosomal protein S6S R Kimball
Department of Cellular and Molecular Physiology, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033, USA
J Biol Chem 274:11647-52. 1999..Thus, leucine acting through an mTOR-dependent pathway stimulates the translation of specific mRNAs both by increasing the availability of eIF4E and by stimulating phosphorylation of S6...
Assessment of cell-signaling pathways in the regulation of mammalian target of rapamycin (mTOR) by amino acids in rat adipocytesP T Pham
Department of Cellular and Molecular Physiology, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033, USA
J Cell Biochem 79:427-41. 2000..Overall, our study emphasizes the need for caution when extending results obtained using established cell lines to the differentiated nondividing cells found in most tissues...
Endotoxin-induced decrease in muscle protein synthesis is associated with changes in eIF2B, eIF4E, and IGF-IC H Lang
Departments of Cellular and Molecular Physiology, and Surgery, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
Am J Physiol Endocrinol Metab 278:E1133-43. 2000....
Subunit assembly and guanine nucleotide exchange activity of eukaryotic initiation factor-2B expressed in Sf9 cellsJ R Fabian
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
J Biol Chem 272:12359-65. 1997..Furthermore, eIF-2Bepsilon is necessary and is perhaps sufficient for GEF activity in vitro...
Eukaryotic initiation factors and protein synthesis after resistance exercise in ratsP A Farrell
Noll Physiological Research Center and Graduate Program in Physiology, Pennsylvania State University, University Park 16802, USA
J Appl Physiol 88:1036-42. 2000..These new data, along with our previous report on eIF2B, suggest that the regulation of peptide chain initiation after exercise is more dependent on eIF2B than on the eIF4E system...
Immediate response of mammalian target of rapamycin (mTOR)-mediated signalling following acute resistance exercise in rat skeletal muscleDouglas R Bolster
The Pennsylvania State University College of Medicine, Department of Cellular and Molecular Physiology, Hershey, PA 17033, USA
J Physiol 553:213-20. 2003....
Contribution of insulin to the translational control of protein synthesis in skeletal muscle by leucineJoshua C Anthony
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
Am J Physiol Endocrinol Metab 282:E1092-101. 2002..In contrast, assembly of the mRNA cap-binding complex occurs independently of increases in insulin and, by itself, is insufficient to stimulate rates of protein synthesis in skeletal muscle after leucine administration...
AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signalingDouglas R Bolster
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
J Biol Chem 277:23977-80. 2002..This is the first investigation to demonstrate changes in translation initiation and skeletal muscle protein synthesis in response to AMPK activation...
Resistance exercise increases muscle protein synthesis and translation of eukaryotic initiation factor 2Bepsilon mRNA in a mammalian target of rapamycin-dependent mannerNeil Kubica
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
J Biol Chem 280:7570-80. 2005..These data suggest a novel link between mTOR signaling and eIF2Bepsilon mRNA translation that could contribute to the stimulation of protein synthesis following acute resistance exercise...
Orally administered leucine enhances protein synthesis in skeletal muscle of diabetic rats in the absence of increases in 4E-BP1 or S6K1 phosphorylationJoshua C Anthony
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
Diabetes 51:928-36. 2002..The insulin-dependent mechanism is associated with increased phosphorylation of 4E-BP1 and S6K1. In contrast, the insulin-independent effect on protein synthesis is mediated by an unknown mechanism...
Signaling pathways involved in translational control of protein synthesis in skeletal muscle by leucineJ C Anthony
Department of Cellular and Molecular Physiology, P.O. Box 850, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
J Nutr 131:856S-860S. 2001..The stimulatory effects of leucine on translation initiation are mediated in part through the protein kinase mammalian target of rapamycin (mTOR), where both insulin signaling and leucine signaling converge to promote a maximal response...
Cloning and characterization of complementary and genomic DNAs encoding the epsilon-subunit of rat translation initiation factor-2BK M Flowers
Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey, PA 17033, USA
Biochim Biophys Acta 1307:318-24. 1996..Examination of the promoter region of the gene reveals a consensus binding site for the alpha-Pal transcription factor as well as possible cytokine-response elements and binding sites for testis-specific transcription factors...
Molecular cloning and characterization of cDNA encoding the alpha subunit of the rat protein synthesis initiation factor eIF-2BK M Flowers
Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey 17033, USA
Proc Natl Acad Sci U S A 92:4274-8. 1995..Southern blots indicate that the eIF-2B alpha cDNA also recognizes genomic DNA fragments from several other species, suggesting significant homology between the rat eIF-2B alpha gene and that from other species...
Hydrogen peroxide impairs insulin-stimulated assembly of mTORC1Lianqin Zhang
Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
Free Radic Biol Med 46:1500-9. 2009..These findings are consistent with PRAS40 functioning as a negative regulator of insulin-stimulated mTORC1 activity during oxidant stress...
Cloning and characterization of cDNA encoding rat hemin-sensitive initiation factor-2 alpha (eIF-2 alpha) kinase. Evidence for multitissue expressionH Mellor
Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey 17033
J Biol Chem 269:10201-4. 1994..These findings raise the possibility of additional, uncharacterized roles for HCR in non-erythroid cells...
Regulation of protein synthesis by branched-chain amino acidsS R Kimball
Department of Cellular and Molecular Physiology, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033, USA
Curr Opin Clin Nutr Metab Care 4:39-43. 2001....
Regulation of eukaryotic initiation factor-2B activity in muscle of diabetic ratsA M Karinch
Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey 17033
Am J Physiol 264:E101-8. 1993..Modulation of casein kinase II activity may be a factor in the regulation of protein synthesis in muscle during acute diabetes. The activity of eIF-2B in heart might be maintained by the increased NADPH/NADP+...
The Src-family tyrosine kinase inhibitor PP1 interferes with the activation of ribosomal protein S6 kinasesO Jameel Shah
Department of Cellular and Molecular Physiology, College of Medicine, The Pennsylvania State University, 500 University Drive, Hershey, PA 17033, U S A
Biochem J 366:57-62. 2002..Thus activation of Src may supply a necessary signal for the activation of p70S6K1 and possibly other S6Ks...
Beta -oxidation of free fatty acids is required to maintain translational control of protein synthesis in heartStephen J Crozier
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
Am J Physiol Endocrinol Metab 283:E1144-50. 2002..Therefore, the activation state of signal transduction pathways that are responsive to cellular energy stress represents one mechanism whereby translation initiation may be regulated in cardiac muscle...
The mTOR signaling pathway mediates control of ribosomal protein mRNA translation in rat liverAli K Reiter
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, P.O. Box 850, Hershey, PA 17033, USA
Int J Biochem Cell Biol 36:2169-79. 2004..The results suggest that in liver in vivo, mTOR-dependent signaling is critical for maximal stimulation of TOP mRNA translation...
Cloning and characterization of a cDNA encoding rat PKR, the double-stranded RNA-dependent eukaryotic initiation factor-2 kinaseH Mellor
Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey 17033
Biochim Biophys Acta 1219:693-6. 1994..In addition, sequence elements in the 5'- and 3'-untranslated regions are also conserved between species...
Assessment of biomarkers of protein anabolism in skeletal muscle during the life span of the rat: sarcopenia despite elevated protein synthesisScot R Kimball
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey 17033, USA
Am J Physiol Endocrinol Metab 287:E772-80. 2004..The results are consistent with a model wherein protein synthesis is enhanced during aging in a futile attempt to maintain muscle mass...
AMPK represses TOP mRNA translation but not global protein synthesis in liverAli K Reiter
Department of Cellular and Molecular Physiology, The Pennsylvania State College of Medicine, PO Box 850, Hershey, PA 17033, USA
Biochem Biophys Res Commun 374:345-50. 2008..Thus, in liver, AMPK activation repressed translation of TOP mRNAs through a mechanism distinct from downregulated phosphorylation of S6K1 or rpS6...
Activation of the mammalian target of rapamycin complex 1 is both necessary and sufficient to stimulate eukaryotic initiation factor 2Bvarepsilon mRNA translation and protein synthesisNeil Kubica
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, United States
Int J Biochem Cell Biol 40:2522-33. 2008....
AMP-activated protein kinase agonists increase mRNA content of the muscle-specific ubiquitin ligases MAFbx and MuRF1 in C2C12 cellsBrian J Krawiec
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, 500 Univ Drive, Hershey, PA 17033, USA
Am J Physiol Endocrinol Metab 292:E1555-67. 2007....
Regulation of global and specific mRNA translation by oral administration of branched-chain amino acidsScot R Kimball
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
Biochem Biophys Res Commun 313:423-7. 2004....
Translational control of protein synthesis: implications for understanding changes in skeletal muscle massL S Jefferson
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey 17033, USA
Int J Sport Nutr Exerc Metab 11:S143-9. 2001..Potential mechanisms for exercise-induced increase in muscle mass are discussed...
Dexamethasone represses signaling through the mammalian target of rapamycin in muscle cells by enhancing expression of REDD1Hongmei Wang
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
J Biol Chem 281:39128-34. 2006..Overall, the data support the conclusion that REDD1 functions upstream of Tuberin and Rheb to down-regulate mTOR signaling in response to dexamethasone...
Regulation of protein synthesis associated with skeletal muscle hypertrophy by insulin-, amino acid- and exercise-induced signallingDouglas R Bolster
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, PO Box 850, Hershey, PA 17033, USA
Proc Nutr Soc 63:351-6. 2004....
Repression of protein synthesis and mTOR signaling in rat liver mediated by the AMPK activator aminoimidazole carboxamide ribonucleosideAli K Reiter
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, P O Box 850, Hershey, PA 17033, USA
Am J Physiol Endocrinol Metab 288:E980-8. 2005..Overall, however, the results from both experimental models support a scenario in which AICAR directly represses protein synthesis and mTOR signaling in the liver through an AMPK-dependent mechanism...
Molecular mechanisms through which amino acids mediate signaling through the mammalian target of rapamycinScot R Kimball
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
Curr Opin Clin Nutr Metab Care 7:39-44. 2004....
Glucagon acts in a dominant manner to repress insulin-induced mammalian target of rapamycin complex 1 signaling in perfused rat liverJamie I Baum
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
Am J Physiol Endocrinol Metab 297:E410-5. 2009..Overall, the results suggest that glucagon acts in a dominant manner to repress insulin-induced mTORC1 signaling, which is in contrast to previous studies showing a dominant action of insulin in the control of hepatic gluconeogenesis...
eIF2alpha kinases GCN2 and PERK modulate transcription and translation of distinct sets of mRNAs in mouse liverAn N Dang Do
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, USA
Physiol Genomics 38:328-41. 2009..These findings open an avenue for more focused future research toward groups of mRNAs that code for the early cellular stress response proteins...
Hormone, cytokine, and nutritional regulation of sepsis-induced increases in atrogin-1 and MuRF1 in skeletal muscleRobert A Frost
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
Am J Physiol Endocrinol Metab 292:E501-12. 2007..Thus, under in vivo conditions in mature adult rats, the sepsis-induced increase in muscle atrogin-1 and MuRF1 mRNA appears both glucocorticoid and TNF independent and is unresponsive to leucine...
Leucine regulates translation initiation in rat skeletal muscle via enhanced eIF4G phosphorylationDouglas R Bolster
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
J Nutr 134:1704-10. 2004..eIF4G assembly and protein synthesis directly in skeletal muscle, possibly by augmenting phosphorylation of eIF4G through a signaling pathway independent of mTOR...
New functions for amino acids: effects on gene transcription and translationScot R Kimball
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033-0850, USA
Am J Clin Nutr 83:500S-507S. 2006....
Invited Review: Role of insulin in translational control of protein synthesis in skeletal muscle by amino acids or exerciseScot R Kimball
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
J Appl Physiol 93:1168-80. 2002..This review summarizes the results of a number of recent studies that have helped to establish our present understanding of the interactions of insulin, amino acids, and exercise in the regulation of protein synthesis in skeletal muscle...
Effects of experimentally induced nephrosis on protein synthesis in rat liverA E Lewandowski
Department of Physiology, College of Medicine, Milton S Hershey Medical Center, Pennsylvania State University, Hershey 17033
Am J Physiol 254:C634-42. 1988..Mechanisms responsible for these alterations include changes in the relative abundance of specific mRNAs and an increase in total cellular RNA...
Hypertrophy of skeletal muscle in diabetic rats in response to chronic resistance exerciseP A Farrell
Noll Physiological Research Center and Department of Kinesiology, University Park, Pennsylvania 16802, USA
J Appl Physiol 87:1075-82. 1999..These data demonstrate that, despite lower circulating insulin concentrations, diabetic rats can increase muscle mass in response to a physiological stimulus...
Glucagon represses signaling through the mammalian target of rapamycin in rat liver by activating AMP-activated protein kinaseScot R Kimball
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
J Biol Chem 279:54103-9. 2004..Amino acids also enhance AMPK phosphorylation, although to a lesser extent than glucagon and amino acids combined...
Effects of alpha-difluoromethylornithine on thrombospondin-1 production by human breast cancer cellsAndrea Manni
Division of Endocrinology, Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
Int J Oncol 31:1187-91. 2007..The reason for this unexpected finding is unknown but may be due to DFMO-induced stimulation of TSP-1 secretion into the systemic circulation, thus preventing its accumulation within the tumor...
Oral leucine administration stimulates protein synthesis in rat skeletal muscleStephen J Crozier
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
J Nutr 135:376-82. 2005..The ability of small doses of leucine to stimulate skeletal muscle protein synthesis suggests that future research on the regulation of skeletal muscle protein synthesis by orally administered leucine will be feasible in humans...
Rapamycin blunts nutrient stimulation of eIF4G, but not PKCepsilon phosphorylation, in skeletal muscleThomas C Vary
Department of Cellular and Molecular Physiology, Rm C4710, Penn State University College of Medicine, H166, 500 University Drive, Hershey, PA 17033, USA
Am J Physiol Endocrinol Metab 293:E188-96. 2007..The latter observation implies that the effects observed with rapamycin were the result of modulation of skeletal muscle signaling mechanisms responsible for eIF4G phosphorylation...
Inhibition of mammalian translation initiation by volatile anestheticsLaura K Palmer
Dept of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, 500 University Dr, Hershey, PA 17033, USA
Am J Physiol Endocrinol Metab 290:E1267-75. 2006..Thus dose- and time-dependent alterations in multiple processes permit liver cells to adapt translation to variable degrees and duration of stress imposed by anesthetic exposure...
Hindlimb casting decreases muscle mass in part by proteasome-dependent proteolysis but independent of protein synthesisBrian J Krawiec
Dept of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA
Am J Physiol Endocrinol Metab 289:E969-80. 2005....
The activated glucocorticoid receptor modulates presumptive autoregulation of ribosomal protein S6 protein kinase, p70 S6KO Jameel Shah
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033-0850, USA
J Biol Chem 277:2525-33. 2002....
Control of protein synthesis by amino acid availabilityScot R Kimball
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, PO Box 850, Hershey, PA 17033, USA
Curr Opin Clin Nutr Metab Care 5:63-7. 2002..In this case, however, the signaling properties and mechanism of action of glutamine remain as an unsolved mystery...
Glucosamine-induced phosphorylation of the alpha-subunit of eukaryotic initiation factor 2 is mediated by the protein kinase R-like endoplasmic-reticulum associated kinaseChristina Leah B Kline
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, 17033, USA
Int J Biochem Cell Biol 38:1004-14. 2006....
Developmental decline in components of signal transduction pathways regulating protein synthesis in pig muscleScot R Kimball
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
Am J Physiol Endocrinol Metab 282:E585-92. 2002..7-day-old neonatal pigs is due in part to decreased content and/or activity of signaling components downstream of PI 3-kinase, e.g., PKB, mTOR, and S6K1...
Leucine is a direct-acting nutrient signal that regulates protein synthesis in adipose tissueChristopher J Lynch
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
Am J Physiol Endocrinol Metab 283:E503-13. 2002..This result implies that leucine or norleucine may acutely stimulate protein synthesis, at least in some tissues, by a mechanism that is independent of both S6K1 and 4E-BP1 phosphorylation...
Exercise-induced alterations in extracellular signal-regulated kinase 1/2 and mammalian target of rapamycin (mTOR) signalling to regulatory mechanisms of mRNA translation in mouse muscleDavid L Williamson
Department of Cellular and Molecular Physiology, H166 The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA
J Physiol 573:497-510. 2006....
Rapid turnover of the mTOR complex 1 (mTORC1) repressor REDD1 and activation of mTORC1 signaling following inhibition of protein synthesisScot R Kimball
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
J Biol Chem 283:3465-75. 2008....
Role of amino acids in the translational control of protein synthesis in mammalsScot R Kimball
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
Semin Cell Dev Biol 16:21-7. 2005..The focus of this article is to review recent studies that have used intact animals as experimental models to examine the role of amino acids as modulators of signal transduction pathways...
Control of translation initiation through integration of signals generated by hormones, nutrients, and exerciseScot R Kimball
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
J Biol Chem 285:29027-32. 2010..Together, modulation of these two regulatory steps in translation initiation accounts in large part for changes in protein synthesis in skeletal muscle produced by the integration of inputs from hormones, nutrients, and exercise...
A microtiter plate assay for assessing the interaction of eukaryotic initiation factor eIF4E with eIF4G and eIF4E binding protein-1Scot R Kimball
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
Anal Biochem 325:364-8. 2004..It also has the advantage that absolute amounts of the individual proteins can be easily estimated. The approach should be applicable to the study of a wide variety of protein-protein interactions...
Ablation of 4E-BP1/2 prevents hyperglycemia-mediated induction of VEGF expression in the rodent retina and in Muller cells in cultureTabitha L Schrufer
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
Diabetes 59:2107-16. 2010..Here, we tested the hypothesis that hyperglycemia mediates induction of VEGF expression in a eukaryotic initiation factor 4E (eIF4E) binding protein (4E-BP) 1 and 2 dependent manner...
Simvastatin represses protein synthesis in the muscle-derived CāCāā cell line with a concomitant reduction in eukaryotic initiation factor 2B expressionAlexander P Tuckow
Dept of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA
Am J Physiol Endocrinol Metab 300:E564-70. 2011..These results suggest that repression of eIF2B expression and activity may contribute, at least in part, to the statin-induced reduction in protein synthesis...
Activation of signaling pathways and regulatory mechanisms of mRNA translation following myocardial ischemia-reperfusionStephen J Crozier
Dept. of Cellular and Molecular Physiology, The Pennsylvania State Univ. College of Medicine, PO Box 850, Hershey, PA 17033, USA
J Appl Physiol 101:576-82. 2006..These changes in protein phosphorylation suggest that control of mRNA translation following ischemia and reperfusion is modulated through a number of signaling pathways and regulatory mechanisms...
Endotoxin induces differential regulation of mTOR-dependent signaling in skeletal muscle and liver of neonatal pigsScot R Kimball
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, 500 University Dr, Hershey, PA 17033, USA
Am J Physiol Endocrinol Metab 285:E637-44. 2003..This finding suggests that the initiator methionyl-tRNA-rather than the mRNA-binding step in translation initiation may play a more critical role in maintaining protein synthesis rates in the neonate during sepsis...
Elevated corticosterone associated with food deprivation upregulates expression in rat skeletal muscle of the mTORC1 repressor, REDD1Nora K McGhee
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
J Nutr 139:828-34. 2009..Overall, the results demonstrate that changes in REDD1 expression likely contribute to the regulation of mTORC1 signaling during food deprivation and refeeding...
Alcohol impairs leucine-mediated phosphorylation of 4E-BP1, S6K1, eIF4G, and mTOR in skeletal muscleCharles H Lang
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
Am J Physiol Endocrinol Metab 285:E1205-15. 2003..Hence, ethanol produces a leucine resistance in skeletal muscle, as evidenced by the impaired phosphorylation of 4E-BP1, eIF4G, S6K1, and mTOR, that is independent of elevations in endogenous glucocorticoids...
Mammalian stress granules represent sites of accumulation of stalled translation initiation complexesScot R Kimball
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
Am J Physiol Cell Physiol 284:C273-84. 2003..Finally, we also show that stress granules contain many, if not all, of the components of the 48S preinitiation complex, but not 60S ribosomal subunits, suggesting that they represent stalled translation initiation complexes...
Melatonin represses oxidative stress-induced activation of the MAP kinase and mTOR signaling pathways in H4IIE hepatoma cells through inhibition of RasScot R Kimball
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
J Pineal Res 44:379-86. 2008..Overall, the results suggest that melatonin acts to prevent many of the H(2)O(2)-induced alterations in the MAPK and mTOR signaling pathways through inhibition of Ras, at least in H4IIE hepatoma cells...
Structure and sequence of the gene encoding the alpha-subunit of rat translation initiation factor-2BK M Flowers
Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey 17033, USA
Biochim Biophys Acta 1264:163-7. 1995....
Severe diabetes inhibits resistance exercise-induced increase in eukaryotic initiation factor 2B activityJ C Kostyak
Noll Physiological Research Center and Department of Kinesiology, Pennsylvania State University, University Park 16802, USA
J Appl Physiol 91:79-84. 2001..05) than in nondiabetic animals. These data suggest that severe hypoinsulinemia is associated with an inability to increase eIF2B activity in response to exercise...
Phosphatidic acid mediates activation of mTORC1 through the ERK signaling pathwayJeremiah N Winter
Department of Cellular and Molecular Physiology, The Pennsylvania State University Collegeof Medicine, Hershey, Pennsylvania 17033, USA
Am J Physiol Cell Physiol 299:C335-44. 2010..Overall, the results demonstrate that leucine and PA signal through parallel pathways to activate mTORC1 and that PA mediates its effect through the ERK pathway, rather than through direct binding to mTOR...
Translational control mechanisms modulate skeletal muscle gene expression during hypertrophyDouglas R Bolster
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, 17033, USA
Exerc Sport Sci Rev 31:111-6. 2003..This review focuses on the importance of mRNA translation in mediating acute increases in protein synthesis after resistance exercise as well as the anabolic response of muscle growth...
Insulin promotes rat retinal neuronal cell survival in a p70S6K-dependent mannerXiaohua Wu
Department of Ophthalmology and Ulerich Ophthalmology Research Center, the JDRF Diabetic Retinopathy Center at Pennsylvania State University, Hershey, PA 17033, USA
J Biol Chem 279:9167-75. 2004..Together, these results suggest that p70S6K plays a key role in insulin stimulated retinal neuronal cell survival...
Acute treatment with TNF-alpha attenuates insulin-stimulated protein synthesis in cultures of C2C12 myotubes through a MEK1-sensitive mechanismDavid L Williamson
Department of Cellular and Molecular Physiology, H166, The Pennsylvania State University College of Medicine, 500 Univ Dr, Hershey, PA 17033, USA
Am J Physiol Endocrinol Metab 289:E95-104. 2005....
Meal feeding alters translational control of gene expression in rat liverAli K Reiter
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
J Nutr 135:367-75. 2005....
Cellular energy status modulates translational control mechanisms in ischemic-reperfused rat heartsStephen J Crozier
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, PO Box 850, Hershey, PA 17033, USA
Am J Physiol Heart Circ Physiol 289:H1242-50. 2005....
Tissue-specific regulation of protein synthesis by insulin and free fatty acidsStephen J Crozier
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
Am J Physiol Endocrinol Metab 285:E754-62. 2003..Thus FFAs may contribute to the translational control of protein synthesis in the heart but not in the gastrocnemius. In contrast, insulin, but not FFAs, is required for the maintenance of protein synthesis in the gastrocnemius...
Ectopic expression of eIF2Bepsilon in rat skeletal muscle rescues the sepsis-induced reduction in guanine nucleotide exchange activity and protein synthesisAlexander P Tuckow
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA
Am J Physiol Endocrinol Metab 299:E241-8. 2010..The results demonstrate that modulation of eIF2Bepsilon expression may be sufficient to correct deficits in skeletal muscle protein synthesis associated with sepsis and other muscle-wasting conditions...
Endotoxin and cisplatin synergistically stimulate TNF-alpha production by renal epithelial cellsGanesan Ramesh
Div of Nephrology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
Am J Physiol Renal Physiol 292:F812-9. 2007..These interactions between cisplatin and endotoxin may be relevant to the pathogenesis of cisplatin nephrotoxicity in humans...
Cardiolipin remodeling by ALCAT1 links oxidative stress and mitochondrial dysfunction to obesityJia Li
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
Cell Metab 12:154-65. 2010..Collectively, these findings identify a key role of ALCAT1 in regulating CL remodeling, mitochondrial dysfunction, and susceptibility to DIO...
ATF4 is necessary and sufficient for ER stress-induced upregulation of REDD1 expressionMichael L Whitney
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, P O Box 850, 500 University Drive, Hershey, PA 17033, USA
Biochem Biophys Res Commun 379:451-5. 2009..Overall, the results suggest that REDD1 expression is upregulated during ER stress through a mechanism involving activation of PERK, phosphorylation of eIF2alpha, and increased ATF4 expression...
Regulation of neonatal liver protein synthesis by insulin and amino acids in pigsScot R Kimball
United States Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, 1100 Bates St, Suite 9064, Houston, TX 77030, USA
Am J Physiol Endocrinol Metab 286:E994-E1003. 2004..The results suggest that amino acids regulate liver protein synthesis in the neonate by modulating the availability of eIF4E for 48S ribosomal complex formation and that this response does not require insulin...
Amino acids do not alter the insulin-induced activation of the insulin signaling pathway in neonatal pigsAgus Suryawan
US Department of Agriculture/Agriculture Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
J Nutr 134:24-30. 2004..Furthermore, amino acids do not alter the insulin-stimulated activation of early steps in the insulin signaling pathway...
Translational control of protein synthesis in muscle and liver of growth hormone-treated pigsJill A Bush
United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA
Endocrinology 144:1273-83. 2003..The results further indicate that the GH-induced protein synthetic response is dependent upon nutritional state and is tissue specific...
Regulation of translation initiation by insulin and amino acids in skeletal muscle of neonatal pigsScot R Kimball
United States Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas 77030, USA
Am J Physiol Endocrinol Metab 285:E40-53. 2003..Thus insulin and amino acids regulate muscle protein synthesis in skeletal muscle of neonates by modulating the availability of eIF4E for 48S ribosomal complex assembly, although other processes also must be involved...
Research Grants
- REGULATION OF SKELETAL MUSCLE METABOLISMLeonard S Jefferson; Fiscal Year: 2010....
- RESEARCH TRAINING IN PHYSIOLOGICAL ADAPTATION TO STRESSLeonard Jefferson; Fiscal Year: 2005..abstract_text> ..
- REGULATION OF SKELETAL MUSCLE METABOLISMLeonard Jefferson; Fiscal Year: 2004..abstract_text> ..
- REGULATION OF LIVER GROWTH AND FUNCTIONLeonard Jefferson; Fiscal Year: 2004..Overall, the studies described in this proposal should provide new insights into the biochemical and molecular mechanisms involved in the regulation of protein synthesis by liver. ..
- REGULATION OF LIVER GROWTH AND FUNCTIONLeonard Jefferson; Fiscal Year: 2007..We expect to identify novel targets for therapeutic intervention under conditions in which the liver contributes to dysregulated metabolism. ..
- REGULATION OF LIVER GROWTH AND FUNCTIONLeonard Jefferson; Fiscal Year: 2009..We expect to identify novel targets for therapeutic intervention under conditions in which the liver contributes to dysregulated metabolism. ..
- REGULATION OF SKELETAL MUSCLE METABOLISMLeonard S Jefferson; Fiscal Year: 2010....
- REGULATION OF LIVER GROWTH AND FUNCTIONLeonard S Jefferson; Fiscal Year: 2010..Knowledge gained from the project will provide insight into designing strategies for treatment of pathologies resulting from the maladapted whole body metabolism associated with obesity and diabetes. ..
- REGULATION OF SKELETAL MUSCLE METABOLISMLeonard Jefferson; Fiscal Year: 2009....
- REGULATION OF LIVER GROWTH AND FUNCTIONLeonard Jefferson; Fiscal Year: 2009..We expect to identify novel targets for therapeutic intervention under conditions in which the liver contributes to dysregulated metabolism. ..
- REGULATION OF SKELETAL MUSCLE METABOLISMLeonard Jefferson; Fiscal Year: 2007....
- REGULATION OF SKELETAL MUSCLE METABOLISMLeonard Jefferson; Fiscal Year: 1993..They should also provide new insights into the biochemical and molecular mechanisms involved in the initiation of protein synthesis...
- REGULATION OF LIVER GROWTH AND FUNCTIONLeonard Jefferson; Fiscal Year: 1999..They should also provide new insights into the biochemical and molecular mechanisms involved in the initiation of protein synthesis. ..
- REGULATION OF SKELETAL MUSCLE METABOLISMLeonard Jefferson; Fiscal Year: 1991..They should also provide new insights into biochemical events involved in peptide-chain initiation...
- REGULATION OF SKELETAL MUSCLE METABOLISMLeonard Jefferson; Fiscal Year: 1999..They should also provide new insights into the biochemical and molecular mechanisms involved in translation initiation. ..
