1University of Illinois Chicago, School of Kinesiology, Chicago, Illinois; and 2University of Kentucky, Department of Physiology, Lexington, Kentucky
Submitted 3 March 2005 ; accepted in final form 8 May 2005
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
lymphocyte enhancement factor-1; glycogen synthase kinase-3; paired like homeodomain transcription factor-2; c-Myc
The classic identifier of Wnt signaling is the accumulation and thus activation of -catenin function (32, 59).
-Catenin is a multifunctional protein that can act in the cytoplasm to link cadherins to the actin cytoskeleton or enter the nucleus and function as a transcription factor (7, 33, 48). In the absence of Wnt signaling, free
-catenin is phosphorylated by glycogen synthase kinase-3
(GSK-3
) and rapidly targeted for proteosomal degradation (2, 14, 20, 26, 27). On Wnt activation, Wnt ligands bind Frizzled (Fzd) and low-density lipoprotein receptor-related protein-5 or -6 coreceptors, stimulate phosphorylation of the protein disheveled (Dvl), and thereby inhibit
-catenin degradation (23, 25, 34). Whereas the exact mechanism is unknown, Dvl phosphorylation/activation is thought to block GSK-3
activity by sequestering GSK-3
via the inhibitory protein frequently rearranged in advanced T cell lymphomas (Frat) (6, 26, 54, 59).
Alternatively, GSK-3 inhibition via phosphorylation at the Ser9 site can increase
-catenin accumulation independent of Wnt signaling (13, 16, 49). Several signaling pathways have been shown to induce GSK-3
phosphorylation in other cell types (22, 60, 61). However, studies of GSK-3
phosphorylation in skeletal muscle have focused on the activation of the phosphatidylinositol 3-kinase/Akt pathway via insulin and/or insulin-like growth factor-1 (IGF-1) (42, 44, 57). Interestingly, both IGF-1 signaling and Akt activation have been linked to skeletal muscle hypertrophy, whereas GSK-3
activity has been shown to be a negative regulator of this process (9, 16, 42). In support of this model, Akt-mediated GSK-3
phosporylation was shown to activate
-catenin during cardiomyocyte hypertrophy (15).
Activated -catenin is associated with cellular growth through its well-characterized function as a transcription factor (32, 33). In the nucleus,
-catenin can form a transcriptional complex with T cell factor/lymphocyte-enhancement factor-1 (Lef-1) family members and subsequently promote expression of target genes (33, 40). Two important transcriptional targets of active
-catenin in developmental and oncogenic growth are c-Myc and cyclin D1 (17, 50). Besides direct transcriptional activation,
-catenin can induce c-Myc and cyclin D1 indirectly through paired-like homeodomain transcription factor2 (Pitx2) activation. Pitx2 has been shown to directly activate c-Myc and cyclin D1 in skeletal muscle cells exposed to Wnt/
-catenin stimulation in vitro (5). Both c-Myc and cyclin D1 are thought to function as cell cycle regulators but recent evidence suggests these proteins can regulate cell size (18, 31, 36, 41). For example, overexpression of c-Myc has been shown to be sufficient to induce hypertrophy in both postmitotic cardiac myocytes and hepatocytes in vivo (24, 62).
The overall goal of this study was to examine the regulation of -catenin during overload-induced skeletal muscle hypertrophy. The hypotheses tested were 1)
-catenin will be activated during overload-induced skeletal muscle hypertrophy, 2) increased
-catenin levels will result from phosphorylation-induced GSK-3
inhibition and not via Wnt signaling, and 3)
-catenin activation will correspond to an induction of known target genes associated with growth control. The results of this study demonstrate that
-catenin is activated and its transcriptional targets are induced during skeletal muscle hypertrophy. The Wnt pathway is implicated as the predominant mediator of
-catenin function during skeletal muscle growth because 1) several markers of Wnt pathway activation are identified following synergist ablation and 2) the
-catenin accumulation is detected at a time in which levels of unphosphorylated GSK-3
(active GSK-3
) are significantly increased.
![]() |
MATERIALS AND METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Preparation of protein samples.
For the analyses of protein expression, whole cell extracts were prepared by homogenizing muscles from control and overloaded mice by a polytron in 750 µl or 1 ml of buffer, respectively, containing 20 mmol/l Tris (pH 7.5), 150 mmol/l NaCl, 1 mmol/l EDTA, 1 mmol/l EGTA, 10 g/l Nonidet P-40, 2.5 mmol/l sodium pyrophosphate, 1 mmol/l -glycerolphosphate, 1 mmol/l sodium orthovanadate, 1 mg/l leupeptin, and 1 mmol/l phenylmethylsulfonyl fluoride. For the analyses of nuclear proteins, extracts were prepared using the nuclear protein isolation kit (NE-PER, Pierce Biotechnology, Rockford, IL) according to the manufacturer's instructions. Briefly, control and overloaded muscles were homogenized in 750 µl or 1 ml of cytoplasmic extraction reagent and centrifuged at 5,000 rpm for 6 min. The supernatant, consisting of free cytosolic protein, was collected and the remaining pellet was treated with 150 or 200 µl of nuclear extraction reagent. The samples were then centrifuged at 14,000 rpm for 10 min and the supernatant was collected for nuclear proteins. Protein concentrations were determined using the DC protein assay (Bio-Rad Laboratories, Hercules, CA). To verify that the NE-PER kit isolated nuclear proteins without the presence of cytoplasmic proteins, cytoplasmic and nuclear protein isolates were run out on SDS page gels, stained with Coomassie blue, and examined for the presence or absence of the 205 KDa form of myosin heavy chain. As predicted, myosin expression was only detected in the cytoplasmic protein fraction (data not shown).
Western blot analysis.
SDS-PAGE was performed on 7.5% acrylamide gels and proteins were transferred to polyvinylidene difluoride membranes. For these experiments, 40 µg of total or nuclear protein were analyzed with antibodies against -catenin (no. c-2206; Sigma, St. Louis, MO) 1:2,000, Lef-1 (no. L-3275, Sigma) 1:1,000, GSK-3
(no. 610202, BD Transduction Laboratories, San Diego, CA) 1:1,000, phosphorylated (Ser9) GSK-3
(no. 9336S, Cell Signaling, Beverly, MA) 1:1,000, Dvl-1 (no. 06-939, Cell Signaling) 1:1,000, Frat1 (no. ab2533-100, Abcam, Cambridge, MA) 1:1,000, c-Myc (no. sc-788, Santa Cruz Biotechnology, Santa Cruz, CA) 1:500, cyclin D1 (no. sc-718, Santa Cruz) 1:500, Pitx2 (no. sc-8748, Santa Cruz) 1:500, Wnt-10b (no. sc-25524, Santa Cruz) 1:1,000, and mFzd-1 (no. AF1120, R&D Systems, Minneapolis, MN) 1:1,000. Peroxidase-conjugated anti-rabbit (no. PI-1000), mouse (no. PI-2000), and goat (no. PI-9500) secondary antibodies were used (Vector Laboratories, Burlingame, CA) 1:5,000 and blots were visualized with an enhanced chemiluminescence kit (Amersham Pharmacia Biotech, Piscataway, NJ). Densitometric measurements were performed on a FluorS Max Imager using QuantityOne Software (Bio-Rad Laboratories). Representative images and denstitometric values were made from analysis of individual muscle samples (n
6 per group).
Coimmunoprecipitation assays.
Coimmunoprecipitation studies were performed using the Immunoprecipitation Starting Kit (Amersham). Briefly, 300 µg of total protein was precleared with a 50% mixture of A/G beads and incubated with a 1:100 dilution of -catenin or Frat1 antibodies at 4°C with rotation overnight, followed by an additional 1 h treatment with A/G beads. The beads were isolated by centrifugation, washed three times, and boiled in 2x loading buffer containing 20% glycerol, 100 nM Tris, 4% SDS, 0.017% bromophenol blue, and 0.25 M DTT for 10 min. Samples were loaded on SDS-PAGE gels for Western blot analysis as previously described.
Immunohistochemistry. Plantaris muscles were dissected from control or 7-day-old ablated mice, placed in tissue freezing medium (Fisher Scientific, Hanover Park, IL), frozen in isopentane cooled with dry ice, and stored at 80°C. Cross-sections (10 µM thick) were cut at the muscle midbelly and mounted on Superfrost/Plus slides (Fisher Scientific) and allowed to air dry for 60 min. Sections were fixed in acetone for 5 min, washed with 50 mM Tris-buffered saline (TBS) pH 7.6 for 5 min and blocked in 5% fetal bovine serum in TBS for 30 min. Excess blocking reagent was removed and replaced with c-Myc primary antibody, 1:100 in TBS overnight. The sections were next washed 3 x 10 min in TBS containing 0.1% Triton X-100 and treated with a rhodamine-conjugated anti-rabbit secondary antibody (no. 211025-109, Jackson ImmunoResearch Laboratories, West Grove, PA) 1:200 in TBS for 40 min. The sections were washed in the TBS-Triton X-100 mixture and then costained with an anti-dystrophin goat polyclonal antibody (no. sc-7461, Santa Cruz) 1:100 in TBS for 1 h. Sections were washed again before being stained with a FITC-conjugated anti-goat secondary antibody (no. 705-095-003, Jackson) 1:200 in TBS for 40 min. Finally, sections were washed in TBS and then mounted with coverslips with the use of VectaMount (Vector Laboratories). Immunoflourescent images were captured on a Kodak DC290 camera taken with a Nikon Diaphot 200 microscope.
RNA isolation and analysis. Total RNA was extracted by homogenizing muscles in TRIzol reagent (Invitrogen, Carlsbad, CA) following the protocol provided and RNA was obtained and suspended in diethyl pyrocarbonate-treated water. cDNA was synthesized from 0.5 µg total RNA using SuperScript II (Invitrogen) and random hexamer primers. Semiquantitative PCR amplification was performed in a 50 µl reaction buffer containing: 1 µl Taq DNA polymerase, 5 µl 10x buffer with 15 mM MgCl2, and 200 µM each of dNTPs (Promega, Madison, WI) along with 0.1 µg of cDNA and 0.2 mM of primers directed against c-Myc (i) forward 5'-TGCGACGAGGAAGAGAATTT and (ii) reverse 5'-GAATCGGACGAGGTACAGGA that yields a 599-bp product and 18S rRNA (i) forward 5'-AAACGGCTACCACATCCAAG and reverse 5'-ccctcttaatcatggcctca that yields a 481 bp product. PCR was performed using an Epgradient S Mastercycler (Eppendorf, Hamburg, Germany) under the following conditions: denaturation for 30 s at 94°C, annealing for 30 s at 58°C, and extension for 45 s at 72°C. PCR products were resolved by running 15 µl of the PCR reaction products on a 1% agrose and 45 mM Tris-borate-1 mM EDTA) gel containing 3 µg/ml ethidium bromide and visualized under UV light. Images represent analysis of individual muscle samples (n = 6 per group).
Statistical analysis.
Statistical analysis for these studies was performed using a paired Student's t-test or ANOVA for multiple groups. All data are expressed as means ± SE. Differences between groups were considered statistically significant if P 0.05.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
|
-Catenin activation does not require increased GSK-3
phosphorylation.
Numerous studies (28, 61) indicate that
-catenin protein levels are regulated by targeted degradation after GSK-3
-mediated phosphorylation. To determine the role of GSK-3
in
-catenin activation, the amount of total and phosphorylated GSK-3
, at the Ser9 site, was examined in control and overloaded muscle samples. Total GSK-3
protein levels increased 46% (P < 0.02) with 7 days of muscle overload, whereas the amount of phosphorylated GSK-3
did not significantly change (Fig. 3). These results show that during skeletal muscle growth,
-catenin protein levels are significantly increased, whereas there is also a significant increase in the level of unphosphorylated GSK-3
protein.
|
|
Dvl activation can disrupt GSK-3-mediated degradation of
-catenin via activation of the inhibitory protein Frat1 (26). Because increased GSK-3
phosphorylation/inhibition was not detected during muscle overload (Fig. 3), the relationship between GSK-3
and Frat1 was examined in control and overloaded muscle. Frat1 protein levels did not significantly change with overload; however, the interaction between GSK-3
and Frat1 was induced, consistent with Wnt/
-catenin signaling (Fig. 4C).
-Catenin/Lef-1 transcriptional targets are induced.
The observation of increased nuclear
-catenin/Lef-1 complexes during overload (Fig. 2C) suggested potential changes in target gene expression. Several of the known transcriptional targets of
-catenin are growth-associated genes (32, 58). One well-defined growth gene and transcriptional target of active
-catenin/Lef-1 is c-Myc (5, 17, 50). Levels of c-Myc mRNA, examined by semiquantitative RT-PCR, were undetectable in control muscle (45 cycles) but significantly expressed in muscle after 7 days of overload (Fig. 5). No c-Myc product was detected in control muscle samples with up to 50 cycles (data not shown).
|
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Mechanical overload of skeletal muscle is associated with Wnt activation, characterized by -catenin accumulation accompanied with increases in mFzd-1, Dvl-1, and GSK-3
-Frat1 complex formation. In contrast to the findings in cardiomyocytes, the results of this study argue that the Wnt pathway, and not phosphorylation of GSK-3
, is the more dominant pathway affecting
-catenin activation in response to skeletal muscle overload. In fact,
-catenin accumulation was associated with increased levels of unphosphorylated GSK-3
that would normally predict decreased
-catenin expression. Thus while this study cannot rule out a role for GSK-3
phosphorylation during skeletal muscle hypertrophy, the findings suggest that it is likely not the dominant mechanism responsible for induction of
-catenin protein in mouse skeletal muscle after synergist ablation.
The lack of a change in GSK-3 phosphorylation in the mouse plantaris muscle after synergist ablation is in contrast to the findings of Bodine et al. (9), in which GSK-3
phosphorylation was increased after mechanical overload of the rat plantaris muscle. One potential explanation is that the antibody used in the Bodine study recognizes phosphorylation of both GSK-3
and GSK-3
at Ser21 and Ser9 sites so the increased phosphorylation detected in the previous study could reflect changes in GSK-3
(9). Second, the measurement of phosphorylated GSK-3
in this study was done at a 7 days, whereas the previous work examined GSK-3 phosphorylation after 14 days of overload, making the timecourse a potential source of the difference (9). Finally, because GSK-3
is a multifunctional kinase with many forms of regulation, it is possible that mice and rats have intrinsic and yet unidentified differences in GSK-3
regulation during overload-induced skeletal muscle growth (30, 60).
Although other Wnt proteins may be involved, no change was detected in Wnt-10b protein levels, suggesting that induction of other signaling components mediate Wnt pathway activation in response to skeletal muscle overload. The increase in mFzd-1 protein levels observed in this study are consistent with findings from Carson et al. (10), which showed significant induction of mFzd-1 mRNA levels at 3 days after mechanical overload in rat soleus muscle (10, 43). Increased Dvl-1 expression after skeletal muscle overload is also consistent with Wnt-induced -catenin activation. In some forms of cancer, total Dvl protein levels directly correlate with
-catenin activation (56). However, Wnt activation is generally associated with the hyperphosphorylation of Dvl, characterized by a decreasing mobility in SDS-PAGE gels (23, 25, 34). In this study, Dvl-1 protein levels, including the phosphorylated forms of higher molecular weight, are elevated after skeletal muscle overload (Fig. 4B). Therefore, increasing levels of phosphorylated Dvl-1 protein may be critical for Wnt-induced
-catenin activation during skeletal muscle growth.
An important finding of this study is the induction of Lef-1 protein and the formation of a -catenin-Lef-1 complex with overload. As expected, known
-catenin/Lef-1 transcriptional targets c-Myc, cyclin D1, and Pitx2 were induced during skeletal muscle overload. c-Myc and cyclin D1 are well known for their roles in cell-cycle regulation but recent studies (31, 46) demonstrate that they are critical for the regulation of cell size. While the function of these genes has not been tested, many models of hypertrophic growth report increased c-Myc and cyclin D1 gene expression (1, 10, 11). One potential downstream function could be their role in regulated ribosomal biogenesis, which is critical for maintaining increased rates of protein synthesis (4, 11, 24, 39, 41). In this study, c-Myc was induced after overload in both muscle and nonmuscle or satellite cell nuclei. Thus increased levels of c-Myc may be contributing to the proliferation of satellite cells and other nonmuscle cells, such as fibroblasts and/or endothelial cells.
In summary, the results from this study demonstrate that -catenin is activated during skeletal muscle overload primarily through Wnt signaling and is not the sole result of phosphorylation-induced GSK-3
inhibition. Wnt-induced
-catenin activation was associated with increased protein expression of many Wnt signaling components, including mFzd-1, Dvl-1, and Lef-1. This indicates that mechanical overload also results in significant increases in the Wnt pathway machinery. The Wnt-induced
-catenin/Lef-1 complex formation detected after mechanical overload is associated with increases in known targets, such as c-Myc and cyclin D, which may contribute to hypertrophic growth. Thus these findings implicate Wnt signaling and the activation of
-catenin as an important response to mechanical overload, which may contribute to the compensatory hypertrophic response.
![]() |
GRANTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
FOOTNOTES |
---|
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
2. Amit S, Hatzubai A, Birman Y, Andersen JS, Ben-Shushan E, Mann M, Ben-Neriah Y, and Alkalay I. Axin-mediated CKI phosphorylation of -catenin at Ser45: a molecular switch for the Wnt pathway. Genes Dev 16: 10661076, 2002.
3. Anakwe K, Robson L, Hadley J, Buxton P, Church V, Allen S, Hartmann C, Harfe B, Nohno T, Brown AM, Evans DJ, and Francis-West P. Wnt signalling regulates myogenic differentiation in the developing avian wing. Development 130: 35033514, 2003.
4. Arabi A, Wu S, Ridderstrale K, Bierhoff H, Shiue C, Fatyol K, Fahlen S, Hydbring P, Soderberg O, Grummt I, Larsson LG, and Wright AP. c-Myc associates with ribosomal DNA and activates RNA polymerase I transcription. Nat Cell Biol 7: 303310, 2005.[CrossRef][ISI][Medline]
5. Baek SH, Kioussi C, Briata P, Wang D, Nguyen HD, Ohgi KA, Glass CK, Wynshaw-Boris A, Rose DW, and Rosenfeld MG. Regulated subset of G1 growth-control genes in response to derepression by the Wnt pathway. Proc Natl Acad Sci USA 100: 32453250, 2003.
6. Bax B, Carter PS, Lewis C, Guy AR, Bridges A, Tanner R, Pettman G, Mannix C, Culbert AA, Brown MJ, Smith DG, and Reith AD. The structure of phosphorylated GSK-3 complexed with a peptide, FRATtide, that inhibits beta-catenin phosphorylation. Structure (Camb) 9: 11431152, 2001.[Medline]
7. Ben-Ze'ev A, Shtutman M, and Zhurinsky J. The integration of cell adhesion with gene expression: the role of beta-catenin. Exp Cell Res 261: 7582, 2000.[CrossRef][ISI][Medline]
8. Billin AN, Thirlwell H, and Ayer DE. -Catenin-histone deacetylase interactions regulate the transition of LEF1 from a transcriptional repressor to an activator. Mol Cell Biol 20: 68826890, 2000.
9. Bodine SC, Stitt TN, Gonzalez M, Kline WO, Stover GL, Bauerlein R, Zlotchenko E, Scrimgeour A, Lawrence JC, Glass DJ, and Yancopoulos GD. Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol 3: 10141019, 2001.[CrossRef][ISI][Medline]
10. Carson JA, Nettleton D, and Reecy JM. Differential gene expression in the rat soleus muscle during early work overload-induced hypertrophy. FASEB J 16: 207209, 2002.
11. Chen YW, Nader GA, Baar KR, Fedele MJ, Hoffman EP, and Esser KA. Response of rat muscle to acute resistance exercise defined by transcriptional and translational profiling. J Physiol 545: 2741, 2002.
12. Cossu G and Borello U. Wnt signaling and the activation of myogenesis in mammals. Embo J 18: 68676872, 1999.
13. Delcommenne M, Tan C, Gray V, Rue L, Woodgett J, and Dedhar S. Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase. Proc Natl Acad Sci USA 95: 1121111216, 1998.
14. Gao ZH, Seeling JM, Hill V, Yochum A, and Virshup DM. Casein kinase I phosphorylates and destabilizes the -catenin degradation complex. Proc Natl Acad Sci USA 99: 11821187, 2002.
15. Haq S, Michael A, Andreucci M, Bhattacharya K, Dotto P, Walters B, Woodgett J, Kilter H, and Force T. Stabilization of -catenin by a Wnt-independent mechanism regulates cardiomyocyte growth. Proc Natl Acad Sci USA 100: 46104615, 2003.
16. Hardt SE and Sadoshima J. Glycogen synthase kinase-3: a novel regulator of cardiac hypertrophy and development. Circ Res 90: 10551063, 2002.
17. He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, and Kinzler KW. Identification of c-MYC as a target of the APC pathway. Science 281: 15091512, 1998.
18. Hesketh JE and Whitelaw PF. The role of cellular oncogenes in myogenesis and muscle cell hypertrophy. Int J Biochem 24: 193203, 1992.[CrossRef][ISI][Medline]
19. Hornberger TA, McLoughlin TJ, Leszczynski JK, Armstrong DD, Jameson RR, Bowen PE, Hwang ES, Hou H, Moustafa ME, Carlson BA, Hatfield DL, Diamond AM, and Esser KA. Selenoprotein-deficient transgenic mice exhibit enhanced exercise-induced muscle growth. J Nutr 133: 30913097, 2003.
20. Ikeda S, Kishida S, Yamamoto H, Murai H, Koyama S, and Kikuchi A. Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3 and
-catenin and promotes GSK-3
-dependent phosphorylation of
-catenin. Embo J 17: 13711384, 1998.
21. Ikeya M and Takada S. Wnt signaling from the dorsal neural tube is required for the formation of the medial dermomyotome. Development 125: 49694976, 1998.
22. Kang UG, Seo MS, Roh MS, Kim Y, Yoon SC, and Kim YS. The effects of clozapine on the GSK-3-mediated signaling pathway. FEBS Lett 560: 115119, 2004.[CrossRef][ISI][Medline]
23. Karasawa T, Yokokura H, Kitajewski J, and Lombroso PJ. Frizzled-9 is activated by Wnt-2 and functions in Wnt/-catenin signaling. J Biol Chem 277: 3747937486, 2002.
24. Kim S, Li Q, Dang CV, and Lee LA. Induction of ribosomal genes and hepatocyte hypertrophy by adenovirus-mediated expression of c-Myc in vivo. Proc Natl Acad Sci USA 97: 1119811202, 2000.
25. Lee JS, Ishimoto A, and Yanagawa S. Characterization of mouse dishevelled (Dvl) proteins in Wnt/Wingless signaling pathway. J Biol Chem 274: 2146421470, 1999.
26. Li L, Yuan H, Weaver CD, Mao J, Farr GH 3rd, Sussman DJ, Jonkers J, Kimelman D, and Wu D. Axin and Frat1 interact with dvl and GSK, bridging Dvl to GSK in Wnt-mediated regulation of LEF-1. EMBO J 18: 42334240, 1999.
27. Liu C, Kato Y, Zhang Z, Do VM, Yankner BA, and He X. -Trcp couples
-catenin phosphorylation-degradation and regulates Xenopus axis formation. Proc Natl Acad Sci USA 96: 62736278, 1999.
28. Liu C, Li Y, Semenov M, Han C, Baeg GH, Tan Y, Zhang Z, Lin X, and He X. Control of -catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 108: 837847, 2002.[CrossRef][ISI][Medline]
29. Luo Z, Wang Q, Dobbins GC, Levy S, Xiong WC, and Mei L. Signaling complexes for postsynaptic differentiation. J Neurocytol 32: 697708, 2003.[CrossRef][ISI][Medline]
30. Michael A, Haq S, Chen X, Hsich E, Cui L, Walters B, Shao Z, Bhattacharya K, Kilter H, Huggins G, Andreucci M, Periasamy M, Solomon RN, Liao R, Patten R, Molkentin JD, and Force T. Glycogen synthase kinase-3 regulates growth, calcium homeostasis, and diastolic function in the heart. J Biol Chem 279: 2138321393, 2004.
31. Montagne J. Genetic and molecular mechanisms of cell size control. Molecular Cell Biol Res Commun 4: 195202, 2000.[CrossRef]
32. Moon RT, Bowerman B, Boutros M, and Perrimon N. The promise and perils of Wnt signaling through -catenin. Science 296: 16441646, 2002.
33. Novak A and Dedhar S. Signaling through -catenin and Lef/Tcf. Cell Molec Life Sci 56: 523537, 1999.[CrossRef][ISI][Medline]
34. Pan WJ, Pang SZ, Huang T, Guo HY, Wu D, and Li L. Characterization of function of three domains in dishevelled-1: DEP domain is responsible for membrane translocation of dishevelled-1. Cell Res 14: 324330, 2004.[ISI][Medline]
35. Petropoulos H and Skerjanc IS. Beta-catenin is essential and sufficient for skeletal myogenesis in P19 cells. J Biological Chem 277: 1539315399, 2002.
36. Piedra ME, Delgado MD, Ros MA, and Leon J. c-Myc overexpression increases cell size and impairs cartilage differentiation during chick limb development. Cell Growth Differ 13: 185193, 2002.
37. Pizzuti A, Amati F, Calabrese G, Mari A, Colosimo A, Silani V, Giardino L, Ratti A, Penso D, Calza L, Palka G, Scarlato G, Novelli G, and Dallapiccola B. cDNA characterization and chromosomal mapping of two human homologues of the Drosophila dishevelled polarity gene. Hum Mol Genet 5: 953958, 1996.
38. Polesskaya A, Seale P, and Rudnicki MA. Wnt signaling induces the myogenic specification of resident CD45+ adult stem cells during muscle regeneration. Cell 113: 841852, 2003.[CrossRef][ISI][Medline]
39. Pollack PS, Houser SR, Budjak R, and Goldman B. c-Myc gene expression is localized to the myocyte following hemodynamic overload in vivo. J Cell Biochem 54: 7884, 1994.[CrossRef][ISI][Medline]
40. Porfiri E, Rubinfeld B, Albert I, Hovanes K, Waterman M, and Polakis P. Induction of a -catenin-LEF-1 complex by wnt-1 and transforming mutants of
-catenin. Oncogene 15: 28332839, 1997.[CrossRef][ISI][Medline]
41. Prober DA and Edgar BA. Growth regulation by oncogenesnew insights from model organisms. Current Opinion Genet Devel 11: 1926, 2001.[CrossRef][ISI]
42. Rommel C, Bodine SC, Clarke BA, Rossman R, Nunez L, Stitt TN, Yancopoulos GD, and Glass DJ. Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways. Nature Cell Biol 3: 10091013, 2001.[CrossRef][ISI][Medline]
43. Sagara N, Toda G, Hirai M, Terada M, and Katoh M. Molecular cloning, differential expression, and chromosomal localization of human frizzled-1, frizzled-2, and frizzled-7. Biochem Biophys Res Commun 252: 117122, 1998.[CrossRef][ISI][Medline]
44. Sakamoto K, Arnolds DE, Ekberg I, Thorell A, and Goodyear LJ. Exercise regulates Akt and glycogen synthase kinase-3 activities in human skeletal muscle. Biochem Biophys Res Commun 319: 419425, 2004.[CrossRef][ISI][Medline]
45. Schmidt M, Tanaka M, and Munsterberg A. Expression of ()-catenin in the developing chick myotome is regulated by myogenic signals. Development 127: 41054113, 2000.
46. Schuhmacher M, Staege MS, Pajic A, Polack A, Weidle UH, Bornkamm GW, Eick D, and Kohlhuber F. Control of cell growth by c-Myc in the absence of cell division. Curr Biol 9: 12551258, 1999.[CrossRef][ISI][Medline]
47. Seale P, Polesskaya A, and Rudnicki MA. Adult stem cell specification by Wnt signaling in muscle regeneration. Cell Cycle 2: 418419, 2003.[Medline]
48. Shapiro L. The multi-talented -catenin makes its first appearance. Structure 5: 12651268, 1997.[CrossRef][ISI][Medline]
49. Sharma M, Chuang WW, and Sun Z. Phosphatidylinositol 3-kinase/Akt stimulates androgen pathway through GSK3 inhibition and nuclear
-catenin accumulation. J Biol Chem 277: 3093530941, 2002.
50. Shtutman M, Zhurinsky J, Simcha I, Albanese C, D'Amico M, Pestell R, and Ben-Ze'ev A. The cyclin D1 gene is a target of the -catenin/LEF-1 pathway. Proc Natl Acad Sci USA 96: 55225527, 1999.
51. Snider L and Tapscott SJ. Emerging parallels in the generation and regeneration of skeletal muscle. Cell 113: 811812, 2003.[CrossRef][ISI][Medline]
52. Tajbakhsh S, Borello U, Vivarelli E, Kelly R, Papkoff J, Duprez D, Buckingham M, and Cossu G. Differential activation of Myf5 and MyoD by different Wnts in explants of mouse paraxial mesoderm and the later activation of myogenesis in the absence of Myf5. Development 125: 41554162, 1998.
53. Taylor-Jones JM, McGehee RE, Rando TA, Lecka-Czernik B, Lipschitz DA, and Peterson CA. Activation of an adipogenic program in adult myoblasts with age. Mechanisms Ageing Develop 123: 649661, 2002.[CrossRef][ISI]
54. Thomas GM, Frame S, Goedert M, Nathke I, Polakis P, and Cohen P. A GSK3-binding peptide from FRAT1 selectively inhibits the GSK3-catalysed phosphorylation of axin and beta-catenin. FEBS Lett 458: 247251, 1999.[CrossRef][ISI][Medline]
55. Timson BF. Evaluation of animal models for the study of exercise-induced muscle enlargement. J Applied Physiol 69: 19351945, 1990.
56. Uematsu K, Kanazawa S, You L, He B, Xu Z, Li K, Peterlin BM, McCormick F, and Jablons DM. Wnt pathway activation in mesothelioma: evidence of Dishevelled overexpression and transcriptional activity of -catenin. Cancer Res 63: 45474551, 2003.
57. Vyas DR, Spangenburg EE, Abraha TW, Childs TE, and Booth FW. GSK-3 negatively regulates skeletal myotube hypertrophy. Am J Physiol Cell Physiol 283: C545C551, 2002.
58. Willert J, Epping M, Pollack JR, Brown PO, and Nusse R. A transcriptional response to Wnt protein in human embryonic carcinoma cells. BMC Dev Biol 2: 8, 2002.[CrossRef][Medline]
59. Willert K and Nusse R. Beta-catenin: a key mediator of Wnt signaling. Curr Opin Genet Dev 8: 95102, 1998.[CrossRef][ISI][Medline]
60. Woodgett JR. Judging a protein by more than its name: GSK-3. Sci STKE 2001: RE12, 2001.[Medline]
61. Woodgett JR. Physiological roles of glycogen synthase kinase-3: potential as a therapeutic target for diabetes and other disorders. Curr Drug Targets Immune Endocr Metabol Disord 3: 281290, 2003.[CrossRef][Medline]
62. Xiao G, Mao S, Baumgarten G, Serrano J, Jordan MC, Roos KP, Fishbein MC, and MacLellan WR. Inducible activation of c-Myc in adult myocardium in vivo provokes cardiac myocyte hypertrophy and reactivation of DNA synthesis. Circ Res 89: 11221129, 2001.
|
HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Visit Other APS Journals Online |