Functions of the TGFβ superfamily in human embryonic stem cells

APMIS

Volumn 113, Issue 11-12, 2005, Pages 773-789

  Valdimarsdottir, Gudrun ^a   Mummery, Christine ^b  

^a UNIVERSITY OF ICELAND   (Iceland)

^b HUBRECHT INSTITUTE   (Netherlands)

Author keywords

Differentiation; Embryonic stem cells; Self renewal; TGF signalling; Transcription factors

Indexed keywords

ACTIVIN A; BONE MORPHOGENETIC PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE; PROTEIN NODAL; SMAD PROTEIN; SMAD1 PROTEIN; SMAD2 PROTEIN; SMAD3 PROTEIN; SMAD5 PROTEIN; SMAD8 PROTEIN; TRANSCRIPTION FACTOR; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA1;

CARDIOMYOPATHY; CELL CULTURE; CELL DIFFERENTIATION; CELL ISOLATION; CELL LINEAGE; CELL PROLIFERATION; CELL RENEWAL; CULTURE MEDIUM; DIABETES MELLITUS; EMBRYONIC STEM CELL; ENZYME PHOSPHORYLATION; GENE ACTIVATION; GENE ACTIVITY; GENE EXPRESSION REGULATION; GENE FUNCTION; GENE TARGETING; HUMAN; MULTIGENE FAMILY; NONHUMAN; PARKINSON DISEASE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN INDUCTION; REVIEW; SIGNAL TRANSDUCTION; STEM CELL TRANSPLANTATION; TRANSCRIPTION REGULATION; AMINO ACID SEQUENCE; ANIMAL; COMPARATIVE STUDY; CYTOLOGY; EMBRYO; GENE EXPRESSION; GENETICS; METABOLISM; MOLECULAR GENETICS; MOUSE; PHYSIOLOGY; PLURIPOTENT STEM CELL;

AMINO ACID SEQUENCE; ANIMALS; CELL DIFFERENTIATION; CELLS, CULTURED; EMBRYO; GENE EXPRESSION; GENE EXPRESSION REGULATION, DEVELOPMENTAL; HUMANS; MICE; MOLECULAR SEQUENCE DATA; PLURIPOTENT STEM CELLS; SIGNAL TRANSDUCTION; SMAD PROTEINS; TRANSFORMING GROWTH FACTOR BETA;

EID: 33645469939     PISSN: 09034641     EISSN: 16000463     Source Type: Journal    
DOI: 10.1111/j.1600-0463.2005.apm_3181.x     Document Type: Review

References (124)

1. Smith AG. Embryo-derived stem cells: of mice and men. Annu Rev Cell Dev Biol 2001 17 : 435 62.
2. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science 1998 282 : 1145 7.
3. Reubinoff BE, Pera MF, Fong CY, Trounson A, Bongso A. Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nat Biotechnol 2000 18 : 399 404.
4. Passier R, Mummery C. Origin and use of embryonic and adult stem cells in differentiation and tissue repair. Cardiovasc Res 2003 58 : 324 35.
5. Massague J. The transforming growth factor-beta family. Annu Rev Cell Biol 1990 6 : 597 641.
6. Roberts ABSM. The transforming growth factors beta. In : Roberts AB editor. Peptide Growth Factors and their Receptors. New York : Springer-Verlag, 1990 : 419 72.
7. Goumans MJ, Mummery C. Functional analysis of the TGFbeta receptor/Smad pathway through gene ablation in mice. Int J Dev Biol 2000 44 : 253 65.
8. Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM, et al. Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci U S A 1986 83 : 4167 71.
9. Massague J. TGF-beta signal transduction. Annu Rev Biochem 1998 67 : 753 91.
10. Heldin CH, Miyazono K, ten Dijke P. TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature 1997 390 : 465 71.
11. Piek E, Heldin CH, ten Dijke P. Specificity, diversity, and regulation in TGF-beta superfamily signaling. FASEB J 1999 13 : 2105 24.
12. Massague J. How cells read TGF-beta signals. Nat Rev Mol Cell Biol 2000 1 : 169 78.
13. Derynck R, Feng XH. TGF-beta receptor signaling. Biochim Biophys Acta 1997 1333 : F105 F150.
14. Massague J. How cells read TGF-beta signals. Nat Rev Mol Cell Biol 2000 1 : 169 78.
15. Wrana JL, Attisano L, Wieser R, Ventura F, Massague J. Mechanism of activation of the TGF-beta receptor. Nature 1994 370 : 341 7.
16. Heldin CH, Miyazono K, ten Dijke P. TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature 1997 390 : 465 71.
17. Massague J. How cells read TGF-beta signals. Nat Rev Mol Cell Biol 2000 1 : 169 78.
18. Heldin CH, Miyazono K, ten Dijke P. TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature 1997 390 : 465 71.
19. Hart PJ, Deep S, Taylor AB, Shu Z, Hinck CS, Hinck AP. Crystal structure of the human TbetaR2 ectodomain-TGF-beta3 complex. Nat Struct Biol 2002 9 : 203 8.
20. Kirsch T, Sebald W, Dreyer MK. Crystal structure of the BMP-2-BRIA ectodomain complex. Nat Struct Biol 2000 7 : 492 6.
21. Feng XH, Derynck R. A kinase subdomain of transforming growth factor-beta (TGF-beta) type I receptor determines the TGF-beta intracellular signaling specificity. EMBO J 1997 16 : 3912 23.
22. Franzen P, ten Dijke P, Ichijo H, Yamashita H, Schulz P, Heldin CH, et al. Cloning of a TGF beta type I receptor that forms a heteromeric complex with the TGF beta type II receptor. Cell 1993 75 : 681 92.
23. Wrana JL, Attisano L, Wieser R, Ventura F, Massague J. Mechanism of activation of the TGF-beta receptor. Nature 1994 370 : 341 7.
24. Zhang Y, Derynck R. Regulation of Smad signalling by protein associations and signalling crosstalk. Trends Cell Biol 1999 9 : 274 9.
25. Wrana JL, Attisano L. The Smad pathway. Cytokine Growth Factor Rev 2000 11 : 5 13.
26. Macias-Silva M, Abdollah S, Hoodless PA, Pirone R, Attisano L, Wrana JL. MADR2 is a substrate of the TGFbeta receptor and its phosphorylation is required for nuclear accumulation and signaling. Cell 1996 87 : 1215 24.
27. Souchelnytskyi S, Tamaki K, Engstrom U, Wernstedt C, Ten Dijke P, Heldin CH. Phosphorylation of Ser465 and Ser467 in the C terminus of Smad2 mediates interaction with Smad4 and is required for transforming growth factor-beta signaling. J Biol Chem 1997 272 : 28107 15.
28. Hata A, Lo RS, Wotton D, Lagna G, Massague J. Mutations increasing autoinhibition in activate tumour suppressors Smad2 and Smad4. Nature 1997 388 : 82 7.
29. Lo RS, Chen YG, Shi Y, Pavletich NP, Massague J. The L3 loop: a structural motif determining specific interactions between SMAD proteins and TGF-beta receptors. EMBO J 1998 17 : 996 1005.
30. Chen YG, Hata A, Lo RS, Wotton D, Shi Y, Pavletich N, et al. Determinants of specificity in TGF-beta signal transduction. Genes Dev 1998 12 : 2144 52.
31. Persson U, Izumi H, Souchelnytskyi S, Itoh S, Grimsby S, Engstrom U, et al. The L45 loop in type I receptors for TGF-beta family members is a critical determinant in specifying Smad isoform activation. FEBS Lett 1998 434 : 83 7.
32. ten Dijke P, Yamashita H, Ichijo H, Franzen P, Laiho M, Miyazono K, et al. Characterization of type I receptors for transforming growth factor-beta and activin. Science 1994 264 : 101 4.
33. ten Dijke P, Yamashita H, Sampath TK, Reddi AH, Estevez M, Riddle DL, et al. Identification of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4. J Biol Chem 1994 269 : 16985 8.
34. Yamashita H, ten Dijke P, Huylebroeck D, Sampath TK, Andries M, Smith JC, et al. Osteogenic protein-1 binds to activin type II receptors and induces certain activin-like effects. J Cell Biol 1995 130 : 217 26.
35. Chen YG, Massague J. Smad1 recognition and activation by the ALK1 group of transforming growth factor-beta family receptors. J Biol Chem 1999 274 : 3672 7.
36. Oh SP, Seki T, Goss KA, Imamura T, Yi Y, Donahoe PK, et al. Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis. Proc Natl Acad Sci U S A 2000 97 : 2626 31.
37. Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 2003 113 : 685 700.
38. Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 2003 425 : 577 84.
39. Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 2003 113 : 685 700.
40. ten Dijke P, Hill CS. New insights into TGF-β/Smad signalling. Trends Biochem Sci 2004 29 : 265 73.
41. Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 2003 425 : 577 84.
42. Moustakas A, Souchelnytskyi S, Heldin CH. Smad regulation in TGF-beta signal transduction. J Cell Sci 2001 114 Pt 24 4359 69.
43. ten Dijke P, Hill CS. New insights into TGF-β/Smad signalling. Trends Biochem Sci 2004 29 : 265 73.
44. Reguly T, Wrana JL. In or out? The dynamics of Smad nucleocytoplasmic shuttling. Trends Cell Biol 2003 13 : 216 20.
45. Pierreux CE, Nicolas FJ, Hill CS. Transforming growth factor beta-independent shuttling of Smad4 between the cytoplasm and nucleus. Mol Cell Biol 2000 20 : 9041 54.
46. Itoh S, Landstrom M, Hermansson A, Itoh F, Heldin CH, Heldin NE, et al. Transforming growth factor beta1 induces nuclear export of inhibitory Smad7. J Biol Chem 1998 273 : 29195 201.
47. Miyazono K, Suzuki H, Imamura T. Regulation of TGF-beta signaling and its roles in progression of tumors. Cancer Sci 2003 94 : 230 4.
48. Itoh S, Landstrom M, Hermansson A, Itoh F, Heldin CH, Heldin NE, et al. Transforming growth factor beta1 induces nuclear export of inhibitory Smad7. J Biol Chem 1998 273 : 29195 201.
49. Nakao A, Afrakhte M, Moren A, Nakayama T, Christian JL, Heuchel R, et al. Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. Nature 1997 389 : 631 5.
50. Afrakhte M, Moren A, Jossan S, Itoh S, Sampath K, Westermark B, et al. Induction of inhibitory Smad6 and Smad7 mRNA by TGF-beta family members. Biochem Biophys Res Commun 1998 249 : 505 11.
51. Itoh S, Landstrom M, Hermansson A, Itoh F, Heldin CH, Heldin NE, et al. Transforming growth factor beta1 induces nuclear export of inhibitory Smad7. J Biol Chem 1998 273 : 29195 201.
52. Hollnagel A, Oehlmann V, Heymer J, Ruther U, Nordheim A. Id genes are direct targets of bone morphogenetic protein induction in embryonic stem cells. J Biol Chem 1999 274 : 19838 45.
53. Norton JD. ID helix-loop-helix proteins in cell growth, differentiation and tumorigenesis. J Cell Sci 2000 113 ( Pt 22 3897 905.
54. Sikder HA, Devlin MK, Dunlap S, Ryu B, Alani RM. Id proteins in cell growth and tumorigenesis. Cancer Cell 2003 3 : 525 30.
55. Zebedee Z, Hara E. Id proteins in cell cycle control and cellular senescence. Oncogene 2001 20 : 8317 25.
56. Jen Y, Manova K, Benezra R. Expression patterns of Id1, Id2, and Id3 are highly related but distinct from that of Id4 during mouse embryogenesis. Dev Dyn 1996 207 : 235 52.
57. Nogueira MM, Mitjavila-Garcia MT, Le Pesteur F, Filippi MD, Vainchenker W, Dubart KA, et al. Regulation of Id gene expression during embryonic stem cell-derived hematopoietic differentiation. Biochem Biophys Res Commun 2000 276 : 803 12.
58. Ying QL, Nichols J, Chambers I, Smith A. BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3. Cell 2003 115 : 281 92.
59. Xu RH, Chen X, Li DS, Li R, Addicks GC, Glennon C, et al. BMP4 initiates human embryonic stem cell differentiation to trophoblast. Nat Biotechnol 2002 20 : 1261 4.
60. Zeng X, Miura T, Luo Y, Bhattacharya B, Condie B, Chen J, et al. Properties of pluripotent human embryonic stem cells BG01 and BG02. Stem Cells 2004 22 : 292 312.
61. Benezra R, Rafii S, Lyden D. The Id proteins and angiogenesis. Oncogene 2001 20 : 8334 41.
62. Lyden D, Young AZ, Zagzag D, Yan W, Gerald W, O'Reilly R, et al. Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts. Nature 1999 401 : 670 7.
63. Lyden D, Hattori K, Dias S, Costa C, Blaikie P, Butros L, et al. Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 2001 7 : 1194 201.
64. Fraidenraich D, Stillwell E, Romero E, Wilkes D, Manova K, Basson CT, et al. Rescue of cardiac defects in id knockout embryos by injection of embryonic stem cells. Science 2004 306 : 247 52.
65. Sato N, Meijer L, Skaltsounis L, Greengard P, Brivanlou AH. Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor. Nat Med 2004 10 : 55 63.
66. Johansson BM, Wiles MV. Evidence for involvement of activin A and bone morphogenetic protein 4 in mammalian mesoderm and hematopoietic development. Mol Cell Biol 1995 15 : 141 51.
67. Monteiro RM, Sousa Lopes SM, Korchynskyi O, Ten Dijke P, Mummery CL. Spatio-temporal activation of Smad1 and Smad5 in vivo: monitoring transcriptional activity of Smad proteins. J Cell Sci 2004 117 ( Pt 20 4653 63.
68. Pera MF, Andrade J, Houssami S, Reubinoff B, Trounson A, Stanley EG, et al. Regulation of human embryonic stem cell differentiation by BMP-2 and its antagonist noggin. J Cell Sci 2004 117 ( Pt 7 1269 80.
69. Xu RH, Peck RM, Li DS, Feng X, Ludwig T, Thomson JA. Basic FGF and suppression of BMP signaling sustain undifferentiated proliferation of human ES cells. Nat Methods 2005 2 : 185 90.
70. Goumans MJ, Ward-van Oostwaard D, Wianny F, Savatier P, Zwijsen A, Mummery C. Mouse embryonic stem cells with aberrant transforming growth factor beta signalling exhibit impaired differentiation in vitro and in vivo. Differentiation 1998 63 : 101 13.
71. Besser D. Expression of nodal, lefty-a, and lefty-B in undifferentiated human embryonic stem cells requires activation of Smad2/3. J Biol Chem 2004 279 : 45076 84.
72. Wei CL, Miura T, Robson P, Lim SK, Xu XQ, Lee MY, et al. Transcriptome profiling of human and murine ESCs identifies divergent paths required to maintain the stem cell state. Stem Cells 2005 23 : 166 85.
73. Mishina Y, Hanks MC, Miura S, Tallquist MD, Behringer RR. Generation of Bmpr/Alk3 conditional knockout mice. Genesis 2002 32 : 69 72.
74. Qi X, Li TG, Hao J, Hu J, Wang J, Simmons H, et al. BMP4 supports self-renewal of embryonic stem cells by inhibiting mitogen-activated protein kinase pathways. Proc Natl Acad Sci U S A 2004 101 : 6027 32.
75. Sirard C, de la Pompa JL, Elia A, Itie A, Mirtsos C, Cheung A, et al. The tumor suppressor gene Smad4/Dpc4 is required for gastrulation and later for anterior development of the mouse embryo. Genes Dev 1998 12 : 107 19.
76. Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, et al. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 2003 113 : 643 55.
77. Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, et al. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 2003 113 : 631 42.
78. Pan GJ, Pei DQ. Identification of two distinct transactivation domains in the pluripotency sustaining factor nanog. Cell Res 2003 13 : 499 502.
79. Stewart CL, Kaspar P, Brunet LJ, Bhatt H, Gadi I, Kontgen F, et al. Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor. Nature 1992 359 : 76 9.
80. Xu C, Inokuma MS, Denham J, Golds K, Kundu P, Gold JD, et al. Feeder-free growth of undifferentiated human embryonic stem cells. Nat Biotechnol 2001 19 : 971 4.
81. Amit M, Shariki C, Margulets V, Itskovitz-Eldor J. Feeder layer- and serum-free culture of human embryonic stem cells. Biol Reprod 2004 70 : 837 45.
82. Beattie GM, Lopez AD, Bucay N, Hinton A, Firpo MT, King CC, et al. Activin A maintains pluripotency of human embryonic stem cells in the absence of feeder layers. Stem Cells 2005 23 : 489 95.
83. James D, Levine AJ, Besser D, Hemmati-Brivanlou A. TGFbeta/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells. Development 2005 132 : 1273 82.
84. Xu C, Liguori G, Persico MG, Adamson ED. Abrogation of the Cripto gene in mouse leads to failure of postgastrulation morphogenesis and lack of differentiation of cardiomyocytes. Development 1999 126 : 483 94.
85. Caricasole AA, van Schaik RH, Zeinstra LM, Wierikx CD, van Gurp RJ, van den PM, et al. Human growth-differentiation factor 3 (hGDF3): developmental regulation in human teratocarcinoma cell lines and expression in primary testicular germ cell tumours. Oncogene 1998 16 : 95 103.
86. Nishimoto M, Fukushima A, Okuda A, Muramatsu M. The gene for the embryonic stem cell coactivator UTF1 carries a regulatory element which selectively interacts with a complex composed of Oct-3/4 and Sox-2. Mol Cell Biol 1999 19 : 5453 65.
87. Rogers MB, Hosler BA, Gudas LJ. Specific expression of a retinoic acid-regulated, zinc-finger gene, Rex-1, in preimplantation embryos, trophoblast and spermatocytes. Development 1991 113 : 815 24.
88. Okuda A, Fukushima A, Nishimoto M, Orimo A, Yamagishi T, Nabeshima Y, et al. UTF1, a novel transcriptional coactivator expressed in pluripotent embryonic stem cells and extra-embryonic cells. EMBO J 1998 17 : 2019 32.
89. Feraud O, Vittet D. Murine embryonic stem cell in vitro differentiation: applications to the study of vascular development. Histol Histopathol 2003 18 : 191 9.
90. Hoffman LM, Carpenter MK. Characterization and culture of human embryonic stem cells. Nat Biotechnol 2005 23 : 699 708.
91. Pera MF, Filipczyk AA, Hawes SM, Laslett AL. Isolation, characterization, and differentiation of human embryonic stem cells. Methods Enzymol 2003 365 : 429 46.
92. Kramer J, Hegert C, Guan K, Wobus AM, Muller PK, Rohwedel J. Embryonic stem cell-derived chondrogenic differentiation in vitro: activation by BMP-2 and BMP-4. Mech Dev 2000 92 : 193 205.
93. Chadwick K, Wang L, Li L, Menendez P, Murdoch B, Rouleau A, et al. Cytokines and BMP-4 promote hematopoietic differentiation of human embryonic stem cells. Blood 2003 102 : 906 15.
94. Gerecht-Nir S, Dazard JE, Golan-Mashiach M, Osenberg S, Botvinnik A, Amariglio N, et al. Vascular gene expression and phenotypic correlation during differentiation of human embryonic stem cells. Dev Dyn 2005 232 : 487 97.
95. Kaufman DS, Hanson ET, Lewis RL, Auerbach R, Thomson JA. Hematopoietic colony-forming cells derived from human embryonic stem cells. Proc Natl Acad Sci U S A 2001 98 : 10716 21.
96. Levenberg S, Golub JS, Amit M, Itskovitz-Eldor J, Langer R. Endothelial cells derived from human embryonic stem cells. Proc Natl Acad Sci U S A 2002 99 : 4391 6.
97. Brandenberger R, Wei H, Zhang S, Lei S, Murage J, Fisk GJ, et al. Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. Nat Biotechnol 2004 22 : 707 16.
98. Pfendler KC, Catuar CS, Meneses JJ, Pedersen RA. Overexpression of Nodal promotes differentiation of mouse embryonic stem cells into mesoderm and endoderm at the expense of neuroectoderm formation. Stem Cells Dev 2005 14 : 162 72.
99. Rose-John S. GP130 stimulation and the maintenance of stem cells. Trends Biotechnol 2002 20 : 417 9.
100. Branford WW, Yost HJ. Nodal signaling: CrypticLefty mechanism of antagonism decoded. Curr Biol 2004 14 : R341 R343.
101. Vallier L, Reynolds D, Pedersen RA. Nodal inhibits differentiation of human embryonic stem cells along the neuroectodermal default pathway. Dev Biol 2004 275 : 403 21.
102. Sato N, Sanjuan IM, Heke M, Uchida M, Naef F, Brivanlou AH. Molecular signature of human embryonic stem cells and its comparison with the mouse. Dev Biol 2003 260 : 404 13.
103. Abeyta MJ, Clark AT, Rodriguez RT, Bodnar MS, Pera RA, Firpo MT. Unique gene expression signatures of independently-derived human embryonic stem cell lines. Hum Mol Genet 2004 13 : 601 8.
104. Andrews PW, Benvenisty N, McKay R, Pera MF, Rossant J, Semb H, et al. The International Stem Cell Initiative: toward benchmarks for human embryonic stem cell research. Nat Biotechnol 2005 23 : 795 7.
105. Jen Y, Weintraub H, Benezra R. Overexpression of Id protein inhibits the muscle differentiation program: in vivo association of Id with E2A proteins. Genes Dev 1992 6 : 1466 79.
106. Lyden D, Young AZ, Zagzag D, Yan W, Gerald W, O'Reilly R, et al. Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts. Nature 1999 401 : 670 7.
107. Norton JD. ID helix-loop-helix proteins in cell growth, differentiation and tumorigenesis. J Cell Sci 2000 113 ( Pt 22 3897 905.
108. Nakashima K, Yanagisawa M, Arakawa H, Kimura N, Hisatsune T, Kawabata M, et al. Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300. Science 1999 284 : 479 82.
109. Dunn NR, Vincent SD, Oxburgh L, Robertson EJ, Bikoff EK. Combinatorial activities of Smad2 and Smad3 regulate mesoderm formation and patterning in the mouse embryo. Development 2004 131 : 1717 28.
110. Zhang J, Li L. BMP signaling and stem cell regulation. Dev Biol 2005.
111. Hayashida T, Decaestecker M, Schnaper HW. Cross-talk between ERK MAP kinase and Smad signaling pathways enhances TGF-beta-dependent responses in human mesangial cells. FASEB J 2003 17 : 1576 8.
112. Attisano L, Tuen Lee-Hoeflich S. The Smads. Genome Biol 2001 2 : REVIEWS3010.
113. Pera EM, Ikeda A, Eivers E, De Robertis EM. Integration of IGF, FGF, and anti-BMP signals via Smad1 phosphorylation in neural induction. Genes Dev 2003 17 : 3023 8.
114. Massague J. Integration of Smad and MAPK pathways: a link and a linker revisited. Genes Dev 2003 17 : 2993 7.
115. Yamaguchi Y, Mann DM, Ruoslahti E. Negative regulation of transforming growth factor-beta by the proteoglycan decorin. Nature 1990 346 : 281 4.
116. Inman GJ, Nicolas FJ, Callahan JF, Harling JD, Gaster LM, Reith AD, et al. SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7. Mol Pharmacol 2002 62 : 65 74.
117. Chen C, Shen MM. Two modes by which Lefty proteins inhibit nodal signaling. Curr Biol 2004 14 : 618 24.
118. Cheng SK, Olale F, Brivanlou AH, Schier AF. Lefty blocks a subset of TGFbeta signals by antagonizing EGF-CFC coreceptors. PLoS Biol 2004 2 : E30.
119. Mather JP. Follistatins and alpha 2-macroglobulin are soluble binding proteins for inhibin and activin. Horm Res 1996 45 : 207 10.
120. Thomsen GH. Antagonism within and around the organizer: BMP inhibitors in vertebrate body patterning. Trends Genet 1997 13 : 209 11.
121. Hsu DR, Economides AN, Wang X, Eimon PM, Harland RM. The Xenopus dorsalizing factor Gremlin identifies a novel family of secreted proteins that antagonize BMP activities. Mol Cell 1998 1 : 673 83.
122. Vale W, Rivier J, Vaughan J, McClintock R, Corrigan A, Woo W, et al. Purification and characterization of an FSH releasing protein from porcine ovarian follicular fluid. Nature 1986 321 : 776 9.
123. Ling N, Ying SY, Ueno N, Shimasaki S, Esch F, Hotta M, et al. Pituitary FSH is released by a heterodimer of the beta-subunits from the two forms of inhibin. Nature 1986 321 : 779 82.
124. Meijer L, Skaltsounis AL, Magiatis P, Polychronopoulos P, Knockaert M, Leost M, et al. GSK-3-selective inhibitors derived from Tyrian purple indirubins. Chem Biol 2003 10 : 1255 66.