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Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033
3To whom correspondence and reprint requests should be addressed. E-mail: skimball{at}psu.edu.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONTranslation Initiation.Regulation of eIF2Regulation of 4E-BP1...Regulation of TOP mRNA...LITERATURE CITED |
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KEY WORDS: • essential amino acids • protein synthesis • mRNA translation
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONTranslation Initiation.Regulation of eIF2Regulation of 4E-BP1...Regulation of TOP mRNA...LITERATURE CITED |
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Translation Initiation. |
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TOPABSTRACTINTRODUCTIONTranslation Initiation.Regulation of eIF2Regulation of 4E-BP1...Regulation of TOP mRNA...LITERATURE CITED |
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, reviewed in (1
)]. During a subsequent step, the GTP bound to eIF2 is hydrolyzed to GDP, and the eIF2–GDP binary complex is released from the ribosome. For eIF2 to bind met-tRNAi and reform the active ternary complex, the GDP bound to eIF2 must be exchanged for GTP. This guanine nucleotide exchange reaction is catalyzed by a second initiation factor, eIF2B. The best characterized mechanism for regulating eIF2B activity is through phosphorylation of the 
-subunit of eIF2. Phosphorylation of eIF2 converts it from a substrate into a competitive inhibitor of eIF2B, effectively sequestering eIF2B into an inactive complex. Because translation of essentially all mRNAs begins with met-tRNAi, phosphorylation of eIF2 results in a decline in the synthesis of almost all proteins. Two examples of proteins whose synthesis is maintained when eIF2 is phosphorylated are the activating transcription factor, ATF4 (2
), and the cationic amino acid transporter, Cat-1 (3
). In each case, structures present in the 5'-leader sequence of the mRNAs encoding the proteins allow translation to occur in amino acid–deprived cells in which eIF2 is phosphorylated and translation of most mRNAs is repressed. In particular, the ATF4 5'-leader sequence contains multiple open reading frames upstream of the start codon for the protein and the Cat-1 5'-leader contains an internal ribosome entry site. How these structures regulate mRNA translation is described in recent reviews (4
–6
) and the reader is referred to those articles for more information.
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). The proteins that comprise the eIF4F complex are as follows: eIF4A, an RNA helicase; eIF4E, the protein that binds to the m7GTP cap present at the 5'-end of the mRNA; and eIF4G, a scaffolding protein that binds not only eIF4A and eIF4E, but also eIF3 which is bound to the 40S ribosomal subunit. Thus, mRNA binds to the 40S ribosomal subunit through the association of the eIF4F–mRNA complex with the eIF3–40S ribosomal subunit complex. Binding of eIF4E to eIF4G, and thus formation of the active eIF4F complex, is regulated by the reversible interaction of eIF4E with one of the eIF4E binding proteins, 4E-BP1, 4E-BP2 or 4E-BP3. For example, the binding of 4E-BP1 and eIF4G to eIF4E is mutually exclusive. Because the binding of eIF4E to the 40S ribosomal subunit occurs through its interaction with eIF4G, binding of 4E-BP1 to eIF4E precludes binding of the eIF4E–mRNA complex to the 40S ribosomal subunit. Association of 4E-BP1 with eIF4E is controlled by phosphorylation of 4E-BP1, where hyperphosphorylated forms of the protein do not bind to eIF4E but hypophosphorylated forms do. Although translation of most mRNAs is initiated by the binding of the 40S ribosomal subunit to the m7GTP cap, a number of mRNAs are translated in a cap-independent manner. Thus, decreased association of eIF4E with eIF4G represses the synthesis of many, but not all proteins. Moreover, some mRNAs are more sensitive to alterations in eIF4F function than others. In particular, those mRNAs with 5'-leader sequences predicted to form extensive secondary structure exhibit a greater eIF4F dependency than other mRNAs.
In contrast to the above examples of translational regulation, activation of ribosomal protein S6 kinase (S6K1) modulates the translation of a specific subset of mRNAs, those containing a 5'-terminal oligopyrimidine (TOP) motif adjacent to the m7GTP cap structure [reviewed in (8
,9
)]. Although the mechanism by which S6K1 activation enhances translation of TOP mRNAs is still incompletely defined, it is likely that it involves phosphorylation of ribosomal protein S6. In this regard, S6 is located near the mRNA/tRNA binding site on the 40S ribosomal subunit [reviewed in (8
)], and therefore may be optimally positioned for a potential role in selecting mRNA to be translated.
Phosphorylation by Essential Amino Acids.">
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Regulation of eIF2 Phosphorylation by Essential Amino Acids.
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TOPABSTRACTINTRODUCTIONTranslation Initiation.Regulation of eIF2Regulation of 4E-BP1...Regulation of TOP mRNA...LITERATURE CITED |
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phosphorylation and inhibition of eIF2B activity (10
,11
). A similar effect is observed in yeast, where amino acid deprivation causes activation of the eIF2 kinase referred to as Gcn2p and enhanced phosphorylation of eIF2 [reviewed in (1
)]. A mammalian isoform of Gcn2p, mGCN2, has also been identified (12
,13
) and shown to be absolutely required for amino acid starvation–induced eIF2 phosphorylation in mouse embryonic stem cells (2
). However, despite a clear role for eIF2 phosphorylation in the regulation of protein synthesis by amino acids in cells in culture, results from animal studies in vivo have been less definitive. Thus, in both liver and skeletal muscle of food-deprived rats, feeding a protein-containing meal has no effect on either eIF2 phosphorylation or eIF2B activity, even though protein synthesis is upregulated (14
). Moreover, oral administration of leucine to food-deprived rats stimulates protein synthesis in skeletal muscle to values observed in fed rats, with no change in eIF2 phosphorylation or eIF2B activity (15
). In contrast, in livers of young, food-deprived rats, feeding a meal lacking single, essential amino acids results in both an increase in eIF2 phosphorylation and an inhibition of eIF2B activity (16
). Thus, in liver in vivo, provision of an imbalanced mixture of amino acids, but not changes in a complete mixture, enhances eIF2 phosphorylation. Whether provision of imbalanced amino acid mixtures affects eIF2 phosphorylation in other tissues is unknown. |
Regulation of 4E-BP1 Phosphorylation and eIF4F Assembly by Essential Amino Acids. |
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TOPABSTRACTINTRODUCTIONTranslation Initiation.Regulation of eIF2Regulation of 4E-BP1...Regulation of TOP mRNA...LITERATURE CITED |
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,18
). However, in each case, leucine is the most potent of the amino acids in stimulating translation initiation. In contrast, in isolated adipocytes, leucine is the only amino acid that causes phosphorylation of 4E-BP1 in amino acid–deprived cells (19
). Moreover, in L6 myoblasts, deprivation of leucine, but not histidine, promotes dephosphorylation of 4E-BP1 as well as dissociation of the eIF4G–eIF4E complex (20
). Readdition of leucine to deprived myoblasts restores each parameter to control values.
Similar results have been reported in animals in vivo. In either pigs (21
) or rats (14
,15
,22
) subjected to overnight food deprivation, rates of global protein synthesis are reduced in skeletal muscle and liver. Feeding either a complete meal or a meal consisting only of protein rapidly reverses the inhibition, implying that provision of amino acids is crucial in restoring protein synthesis. In this regard, oral administration of leucine has the same effect as a complete meal in stimulating protein synthesis in skeletal muscle of food-deprived rats (15
). The effect is specific for leucine because oral administration of either isoleucine or valine has no effect on protein synthesis (23
).
The feeding-induced stimulation of protein synthesis in both pigs and rats is associated with enhanced phosphorylation of 4E-BP1, dissociation of eIF4E from the inactive 4E-BP1–eIF4E complex and assembly of the active eIF4G–eIF4E complex (14
,15
,21
,22
). Evidence that eIF4F assembly is necessary for the stimulation of protein synthesis caused by feeding is provided by studies using the macrolide immunosuppressant, rapamycin. Rapamycin binds to the FK506 binding protein (FKBP12), and the rapamycin–FKBP12 complex specifically inhibits the activity of a protein kinase referred to as the mammalian target of rapamycin [mTOR, also called RAFT or FRAP, reviewed in (24
)]. In cells in culture, amino acid–stimulated phosphorylation of both 4E-BP1 and S6K1 is inhibited by rapamycin (17
,25
,26
). Moreover, phosphorylation of both proteins is resistant to inhibition by rapamycin in cells expressing an mTOR variant that does not bind the rapamycin–FKBP12 complex (27
–29
). In skeletal muscle of food-deprived rats (23
) or pigs (30
), amino acid–induced phosphorylation of 4E-BP1 is prevented by treatment with rapamycin before feeding. However, the stimulation of protein synthesis and eIF4F complex assembly is only partially prevented by rapamycin, suggesting that additional mechanisms exist for regulating these processes in muscle.
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Regulation of TOP mRNA Translation by Amino Acids. |
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TOPABSTRACTINTRODUCTIONTranslation Initiation.Regulation of eIF2Regulation of 4E-BP1...Regulation of TOP mRNA...LITERATURE CITED |
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)]. Such mRNAs include those encoding ribosomal proteins, elongation factors 1A and 2, and poly(A)-binding protein. Thus, activation of S6K1 results in increased synthesis of many proteins involved in the process of mRNA translation.
In livers of food-deprived rats, both S6K1 and S6 are hypophosphorylated (16
). In addition, the major portion of the mRNAs encoding ribosomal proteins S4, S8 and L26 is not associated with polysomes and therefore is not being translated. In contrast, two mRNAs that do not contain a TOP sequence, e.g., those encoding ß-actin and albumin, exhibit a predominantly polysomal distribution. In response to oral administration of leucine, the mRNAs encoding the ribosomal proteins become polysome-associated, indicating that leucine enhances the translation of these mRNAs. In contrast, isoleucine has a minimal and valine has no effect on the polysomal distribution of ribosomal protein mRNAs. The mechanism by which leucine stimulates translation of mRNAs encoding ribosomal proteins likely involves activation of S6K1 because leucine enhances phosphorylation of both S6K1 and ribosomal protein S6. In contrast, phosphorylation of these two proteins by isoleucine and valine is greatly attenuated compared with leucine administration.
Further evidence that amino acids regulate hepatic TOP mRNA translation in vivo is provided by a recent study (16
) showing that feeding either a complete meal or a complete meal lacking glycine stimulates phosphorylation of S6K1, whereas feeding a meal lacking tryptophan, leucine or all three branched-chain amino acids (BCAA) does not. Furthermore, the proportion of mRNAs encoding ribosomal proteins S4, S8 and L26 associated with polysomes is significantly less in rats fed diets lacking tryptophan, leucine or all three BCAA compared with rats fed the control or glycine-deficient diets. In contrast, the mRNAs encoding ß-actin and albumin are predominantly polysomal under all dietary conditions, although the number of ribosomes associated with these mRNAs is greater in livers of rats fed the control or glycine-deficient diet compared with diets lacking one or more essential amino acids. This result suggests that the translation of non-TOP–containing mRNAs is reduced in livers of animals fed a diet lacking essential amino acids, but the mechanism for the reduction is different from that for the decline in TOP mRNA translation. In this regard, eIF2 phosphorylation is enhanced and eIF2B activity is reduced in livers of animals fed diets lacking essential amino acids, which may explain the reduced translation of non-TOP-containing mRNAs.
The mechanism by which amino acids regulate S6K1 phosphorylation and activation is unclear, but seems to involve mTOR [reviewed in (8
)]. As discussed in the previous section for 4E-BP1, amino acid–induced phosphorylation of S6K1 is blocked by rapamycin in both cells in culture (25
,31
,32
) and in vivo (23
,30
). However, activation of S6K1 requires phosphorylation at multiple serine and threonine residues, few, if any, of which are phosphorylated by mTOR in vitro. Thus, a variety of protein kinases have been shown to be upstream effectors involved in activation of S6K1, including PDK1, protein kinase B, protein kinase C (PKC)
and PKC
.
In summary, in animals in vivo, deprivation of essential amino acids represses protein synthesis by inhibiting several steps in the initiation phase of mRNA translation (Fig. 2
). In livers of food-deprived rats, feeding a meal lacking single, essential amino acids results in phosphorylation of eIF2 and a concomitant reduction in eIF2B activity. These changes result in a decrease in synthesis of almost all proteins. In addition to changes in eIF2 phosphorylation, 4E-BP1 becomes dephosphorylated, binds to eIF4E, and thereby prevents the assembly of the active eIF4F complex. Dephosphorylation of 4E-BP1 also occurs in both liver and muscle during overnight food deprivation and is rapidly reversed after consumption of a protein-containing meal. Although synthesis of many proteins is reduced by disassembly of eIF4F, others are translated by a cap-independent process and are minimally affected by decreased binding of eIF4E to eIF4G. Finally, overnight food deprivation also results in dephosphorylation and decreased activity of S6K1, as well as dephosphorylation of S6. Either oral administration of leucine or feeding a protein-containing meal reverses these changes. Decreased S6K1 activity has little or no effect on the synthesis of most proteins, but instead preferentially represses the translation of TOP mRNAs, i.e., many of the mRNAs encoding components of the translation machinery. Thus, deprivation of essential amino acids not only directly and rapidly represses the synthesis of most proteins, but also potentially results in a reduction in the capacity to synthesize protein.
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FOOTNOTES |
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2 Manuscript received 6 December 2001. Revision accepted 10 February 2002.
4 Abbreviations used: ATF4, activating transcription factor; BCAA, branched-chain amino acids; Cat-1, cationic amino acid transporter; eIF, eukaryotic initiation factors; FKBP12, FK506 binding protein, 12 kDa; S6K1, ribosomal protein S6 kinase; TOP, 5'-terminal oligopyrimidine.
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LITERATURE CITED |
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TOPABSTRACTINTRODUCTIONTranslation Initiation.Regulation of eIF2Regulation of 4E-BP1...Regulation of TOP mRNA...LITERATURE CITED |
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1. Hinnebusch, A. G. (2000) Mechanism and regulation of initiator methionyl-tRNA binding to ribosomes. Sonenberg, N. Hershey, J.W.B. Mathews, M. B. eds. Translational Control of Gene Expression 2000 Cold Spring Harbor Laboratory Press Cold Spring Harbor, NY. .
2. Harding, H. P., Novoa, I., Zhang, Y., Zeng, H., Wek, R. C., Schapira, M. & Ron, D. (2000) Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol. Cell 6:1099-1108.[Medline]
3.
Fernandez, J., Yaman, I., Mishra, R., Merrick, W. C., Snider, M. D., Lamers, W. H. & Hatzoglou, M. (2001) Internal ribosome entry site-mediated translation of a mammalian mRNA is regulated by amino acid availability. J. Biol. Chem. 276:12285-12291.
4. Carter, M. S., Kuhn, K. M. & Sarnow, P. (2000) Cellular internal ribosome entry site elements and the use of cDNA microarrays in their investigation. Sonenberg, N. Hershey, J.W.B. Mathews, M. B. eds. Translational Control of Gene Expression 2000 Cold Spring Harbor Laboratory Press Cold Spring Harbor, NY. .
5. Geballe, A. P. & Sachs, A. B. (2000) Translational control by upstream open reading frames. Sonenberg, N. Hershey, J.W.B. Mathews, M. B. eds. Translational Control of Gene Expression 2000 Cold Spring Harbor Laboratory Press Cold Spring Harbor, NY. .
6.
Morris, D. R. & Geballe, A. P. (2000) Upstream open reading frames as regulators of mRNA translation. Mol. Cell. Biol. 20:8635-8642.
7. Raught, B., Gingras, A.-C. & Sonenberg, N. (2000) Regulation of ribosomal recruitment in eukaryotes. Sonenberg, N. Hershey, J.W.B. Mathews, M. B. eds. Translational Control of Gene Expression 2000 Cold Spring Harbor Laboratory Press Cold Spring Harbor, NY. .
8. Fumagalli, S. & Thomas, G. (2000) S6 phosphorylation and signal transduction. Sonenberg, N. Hershey, J.W.B. Mathews, M. B. eds. Translational Control of Gene Expression 2000 Cold Spring Harbor Laboratory Press Cold Spring Harbor, NY. .
9. Meyuhas, O. & Hornstein, E. (2000) Translational control of TOP mRNAs. Sonenberg, N. Hershey, J.W.B. Mathews, M. B. eds. Translational Control of Gene Expression 2000 Cold Spring Harbor Laboratory Press Cold Spring Harbor, NY. .
10.
Scorsone, K. A., Panniers, R., Rowlands, A. G. & Henshaw, E. C. (1987) Phosphorylation of eukaryotic initiation factor 2 during physiological stresses which affect protein synthesis. J. Biol. Chem. 262:14538-14543.
11. Rowlands, A. G., Montine, K. S., Henshaw, E. C. & Panniers, R. (1988) Physiological stresses inhibit guanine-nucleotide-exchange factor in Ehrlich cells. Eur. J. Biochem. 175:93-99.[Medline]
12.
Berlanga, J. J., Santoyo, J. & de Haro, C. (1999) Characterization of a mammalian homolog of GCN2 eukaryotic initiation factor 2 kinase. Eur. J. Biochem. 265:754-762.[Medline]
13.
Sood, R., Porter, A. C., Olsen, D., Cavener, D. R. & Wek, R. C. (2000) A mammalian homologue of GCN2 protein kinase important for translational control by phosphorylation of eukaryotic initiation factor-2. Genetics 154:787-801.
14. Yoshizawa, F., Kimball, S. R. & Jefferson, L. S. (1997) Modulation of translation initiation in rat skeletal muscle and liver in response to food intake. Biochem. Biophys. Res. Commun. 240:825-831.[Medline]
15.
Anthony, J. C., Anthony, T. G., Kimball, S. R., Vary, T. C. & Jefferson, L. S. (2000) Orally administered leucine stimulates protein synthesis in skeletal muscle of post-absorptive rats in association with increased eIF4F formation. J. Nutr. 130:139-145.
16.
Anthony, T. G., Reiter, A. K., Anthony, J. C., Kimball, S. R. & Jefferson, L. S. (2001) Deficiency of essential dietary amino acids preferentially inhibits mRNA translation of ribosomal proteins in the liver of meal-fed rats. Am. J. Physiol. 281:E430-E439.
17.
Hara, K., Yonezawa, K., Weng, Q.-P., Kozlowski, M. T., Belham, C. & Avruch, J. (1998) Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. J. Biol. Chem. 273:14484-14494.
18. Wang, X., Campbell, L. E., Miller, C. M. & Proud, C. G. (1998) Amino acid availability regulates p70 S6 kinase and multiple translation factors. Biochem. J. 334:261-267.
19.
Fox, H. L., Pham, P. T., Kimball, S. R., Jefferson, L. S. & Lynch, C. J. (1998) Amino acid effects on translational repressor 4E-BP1 are mediated primarily by L-leucine in isolated adipocytes. Am. J. Physiol. 275:C1232-C1238.
20.
Kimball, S. R., Horetsky, R. L. & Jefferson, L. S. (1998) Implication of eIF2B rather than eIF4E in the regulation of global protein synthesis by amino acids in L6 myoblasts. J. Biol. Chem. 273:30945-30953.
21.
Davis, T. A., Nguyen, H. V., Suryawan, A., Bush, J., Jefferson, L. S. & Kimball, S. R. (2000) Developmental changes in the feeding-induced stimulation of translation initiation in muscle of neonatal pigs. Am. J. Physiol. 279:E1226-E1234.
22. Yoshizawa, F., Kido, T. & Nagasawa, T. (1999) Stimulative effect of dietary protein on the phosphorylation of p70 S6 kinase in the skeletal muscle and liver of food-deprived rats. Biosci. Biotechnol. Bioch. 63:1803-1805.
23.
Anthony, J. C., Yoshizawa, F., Anthony, T. G., Vary, T. C., Jefferson, L. S. & Kimball, S. R. (2000) Leucine stimulates translation initiation in skeletal muscle of post-absorptive rats via a rapamycin-sensitive pathway. J. Nutr. 130:2413-2419.
24. Dennis, P. B., Fumagalli, S. & Thomas, G. (1999) Target of rapamycin (TOR): balancing the opposing forces of protein synthesis and degradation. Curr. Opin. Genet. Dev. 9:49-54.[Medline]
25.
Kimball, S. R., Shantz, L. M., Horetsky, R. L. & Jefferson, L. S. (1999) Leucine regulates translation of specific mRNAs in L6 myoblasts through mTOR-mediated changes in availability of eIF4E and phosphorylation of ribosomal protein S6. J. Biol. Chem. 274:11647-11652.
26.
Xu, G., Kwon, G., Marshall, C. A., Lin, T.-A., Lawrence, J. C. & McDaniel, M. L. (1998) Branched-chain amino acids are essential in the regulation of PHAS-I and p70 S6 kinase by pancreatic ß-cells. A possible role in protein translation and mitogenic signaling. J. Biol. Chem. 273:28178-28184.
27. Brown, E. J., Beal, P. A., Keith, C. T., Chen, J., Shin, T. B. & Schreiber, S. L. (1995) Control of p70 S6 kinase by kinase activity of FRAP in vivo. Nature (Lond.) 377:441-446.[Medline]
28.
Hara, K., Yonezawa, K., Kozlowski, M. T., Sugimoto, T., Andrabi, K., Weng, Q. P., Kasuga, M., Nishimoto, I. & Avruch, J. (1997) Regulation of eIF-4E BP1 phosphorylation by mTOR. J. Biol. Chem. 272:26457-26463.
29.
Peterson, R. T., Beal, P. A., Comb, M. J. & Schreiber, S. L. (2000) FKBP12-rapamycin-associated protein (FRAP) autophosphorylates at serine 2481 under translationally repressive conditions. J. Biol. Chem. 275:7416-7423.
30.
Kimball, S. R., Jefferson, L. S. & Davis, T. A. (2000) Feeding stimulates protein synthesis in muscle and liver of neonatal pigs through an mTOR-dependent process. Am. J. Physiol. 279:E1080-E1087.
31.
Fox, H. L., Kimball, S. R., Jefferson, L. S. & Lynch, C. J. (1998) Amino acids stimulate phosphorylation of p70S6k and organization of rat adipocytes into multicellular clusters. Am. J. Physiol. 274:C206-C213.
32. Patti, M.-E., Brambilla, E., Luzi, L., Landaker, E. J. & Kahn, C. R. (1998) Bidirectional modulation of insulin action by amino acids. J. Clin. Investig. 101:1519-1529.[Medline]
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