![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 15, No. 15, pp. 2010-2022, August 1, 2001
1 Division of Molecular Neurobiology, Department of
Neuroscience, Karolinska Institute, S-17177 Stockholm, Sweden;
2 Laboratory of Molecular Vertebrate Embryology, The
Rockefeller University, New York, New York 10021-6399, USA;
3 International Institute of Genetics and Biophysics, CNR,
80125 Naples, Italy
Nodal proteins have crucial roles in mesendoderm formation and
left-right patterning during vertebrate development. The molecular mechanisms of signal transduction by Nodal and related ligands, however, are not fully understood. In this paper, we present
biochemical and functional evidence that the orphan type I
serine/threonine kinase receptor ALK7 acts as a receptor for mouse
Nodal and Xenopus Nodal-related 1 (Xnr1). Receptor
reconstitution experiments indicate that ALK7 collaborates with ActRIIB
to confer responsiveness to Xnr1 and Nodal. Both receptors can
independently bind Xnr1. In addition, Cripto, an extracellular protein
genetically implicated in Nodal signaling, can independently interact
with both Xnr1 and ALK7, and its expression greatly enhances the
ability of ALK7 and ActRIIB to respond to Nodal ligands. The Activin
receptor ALK4 is also able to mediate Nodal signaling but only in the
presence of Cripto, with which it can also interact directly. A
constitutively activated form of ALK7 mimics the mesendoderm-inducing
activity of Xnr1 in Xenopus embryos, whereas a
dominant-negative ALK7 specifically blocks the activities of Nodal and
Xnr1 but has little effect on other related ligands. In contrast, a
dominant-negative ALK4 blocks all mesoderm-inducing ligands tested,
including Nodal, Xnr1, Xnr2, Xnr4, and Activin. In agreement with a
role in Nodal signaling, ALK7 mRNA is localized to the ectodermal and
organizer regions of Xenopus gastrula embryos and is expressed
during early stages of mouse embryonic development. Therefore, our
results indicate that both ALK4 and ALK7 can mediate signal
transduction by Nodal proteins, although ALK7 appears to be a receptor
more specifically dedicated to Nodal signaling.
[Key Words:
Mesendoderm; TGF-
; ActRIIB; Xnr1; Oep; Cripto]
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  O. Andersson, M. Korach-Andre, E. Reissmann, C. F. Ibanez, and P. Bertolino Growth/differentiation factor 3 signals through ALK7 and regulates accumulation of adipose tissue and diet-induced obesity PNAS, May 20, 2008; 105(20): 7252 - 7256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Bertolino, R. Holmberg, E. Reissmann, O. Andersson, P.-O. Berggren, and C. F. Ibanez Activin B receptor ALK7 is a negative regulator of pancreatic {beta}-cell function PNAS, May 20, 2008; 105(20): 7246 - 7251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kawajiri, M. Yashiro, O. Shinto, K. Nakamura, M. Tendo, S. Takemura, M. Node, Y. Hamashima, T. Kajimoto, T. Sawada, et al. A Novel Transforming Growth Factor {beta} Receptor Kinase Inhibitor, A-77, Prevents the Peritoneal Dissemination of Scirrhous Gastric Carcinoma Clin. Cancer Res., May 1, 2008; 14(9): 2850 - 2860. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. D'Andrea, G. L. Liguori, J. A. Le Good, E. Lonardo, O. Andersson, D. B. Constam, M. G. Persico, and G. Minchiotti Cripto promotes A-P axis specification independently of its stimulatory effect on Nodal autoinduction J. Cell Biol., February 6, 2008; 180(3): 597 - 605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. V. Esguerra, L. Nelles, L. Vermeire, A. Ibrahimi, A. D. Crawford, R. Derua, E. Janssens, E. Waelkens, P. Carmeliet, D. Collen, et al. Ttrap is an essential modulator of Smad3-dependent Nodal signaling during zebrafish gastrulation and left-right axis determination Development, December 15, 2007; 134(24): 4381 - 4393. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Chang and R. M. Harland Neural induction requires continued suppression of both Smad1 and Smad2 signals during gastrulation Development, November 1, 2007; 134(21): 3861 - 3872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Wang and B. K Tsang Nodal signalling and apoptosis Reproduction, May 1, 2007; 133(5): 847 - 853. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Shen Nodal signaling: developmental roles and regulation Development, March 15, 2007; 134(6): 1023 - 1034. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Dvash, N. Sharon, O. Yanuka, and N. Benvenisty Molecular Analysis of LEFTY-Expressing Cells in Early Human Embryoid Bodies Stem Cells, February 1, 2007; 25(2): 465 - 472. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Luo, A. H. Lin, E. Masliah, and T. Wyss-Coray Bioluminescence imaging of Smad signaling in living mice shows correlation with excitotoxic neurodegeneration PNAS, November 28, 2006; 103(48): 18326 - 18331. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Wang, J.-Y. Jiang, C. Zhu, C. Peng, and B. K. Tsang Role and Regulation of Nodal/Activin Receptor-Like Kinase 7 Signaling Pathway in the Control of Ovarian Follicular Atresia Mol. Endocrinol., October 1, 2006; 20(10): 2469 - 2482. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Itman, S. Mendis, B. Barakat, and K. L. Loveland All in the family: TGF-{beta} family action in testis development. Reproduction, August 1, 2006; 132(2): 233 - 246. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E.K. Moses, E. Fitzpatrick, K.A. Freed, T.D. Dyer, S. Forrest, K. Elliott, M.P. Johnson, J. Blangero, and S.P. Brennecke Objective prioritization of positional candidate genes at a quantitative trait locus for pre-eclampsia on 2q22 Mol. Hum. Reprod., August 1, 2006; 12(8): 505 - 512. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Mazerbourg and A. J.W. Hsueh Genomic analyses facilitate identification of receptors and signalling pathways for growth differentiation factor 9 and related orphan bone morphogenetic protein/growth differentiation factor ligands Hum. Reprod. Update, July 1, 2006; 12(4): 373 - 383. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Xu, H. Zhou, Q. Wang, N. Auersperg, and C. Peng Activin Receptor-Like Kinase 7 Induces Apoptosis through Up-Regulation of Bax and Down-Regulation of Xiap in Normal and Malignant Ovarian Epithelial Cell Lines Mol. Cancer Res., April 1, 2006; 4(4): 235 - 246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Chen, S. M. Ware, A. Sato, D. E. Houston-Hawkins, R. Habas, M. M. Matzuk, M. M. Shen, and C. W. Brown The Vg1-related protein Gdf3 acts in a Nodal signaling pathway in the pre-gastrulation mouse embryo Development, January 15, 2006; 133(2): 319 - 329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Onuma, C.-Y. Yeo, and M. Whitman XCR2, one of three Xenopus EGF-CFC genes, has a distinct role in the regulation of left-right patterning Development, January 15, 2006; 133(2): 237 - 250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Chu, J. Ding, K. Jeays-Ward, S. M. Price, M. Placzek, and M. M. Shen Non-cell-autonomous role for Cripto in axial midline formation during vertebrate embryogenesis Development, December 15, 2005; 132(24): 5539 - 5551. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Vallier, M. Alexander, and R. A. Pedersen Activin/Nodal and FGF pathways cooperate to maintain pluripotency of human embryonic stem cells J. Cell Sci., October 1, 2005; 118(19): 4495 - 4509. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Mazerbourg, K. Sangkuhl, C.-W. Luo, S. Sudo, C. Klein, and A. J. W. Hsueh Identification of Receptors and Signaling Pathways for Orphan Bone Morphogenetic Protein/Growth Differentiation Factor Ligands Based on Genomic Analyses J. Biol. Chem., September 16, 2005; 280(37): 32122 - 32132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Bamberger, A. Scharer, M. Antsiferova, B. Tychsen, S. Pankow, M. Muller, T. Rulicke, R. Paus, and S. Werner Activin Controls Skin Morphogenesis and Wound Repair Predominantly via Stromal Cells and in a Concentration-Dependent Manner via Keratinocytes Am. J. Pathol., September 1, 2005; 167(3): 733 - 747. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. Lin, J. Luo, L. H. Mondshein, P. ten Dijke, D. Vivien, C. H. Contag, and T. Wyss-Coray Global Analysis of Smad2/3-Dependent TGF-{beta} Signaling in Living Mice Reveals Prominent Tissue-Specific Responses to Injury J. Immunol., July 1, 2005; 175(1): 547 - 554. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Parish, S. Parisi, M. G. Persico, E. Arenas, and G. Minchiotti Cripto as a Target for Improving Embryonic Stem Cell-Based Therapy in Parkinson's Disease Stem Cells, April 1, 2005; 23(4): 471 - 476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Jornvall, E. Reissmann, O. Andersson, M. Mehrkash, and C. F. Ibanez ALK7, a Receptor for Nodal, Is Dispensable for Embryogenesis and Left-Right Patterning in the Mouse Mol. Cell. Biol., November 1, 2004; 24(21): 9383 - 9389. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Xu, Y. Zhong, S. Munir, B. B. Yang, B. K. Tsang, and C. Peng Nodal Induces Apoptosis and Inhibits Proliferation in Human Epithelial Ovarian Cancer Cells via Activin Receptor-Like Kinase 7 J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5523 - 5534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Munir, G. Xu, Y. Wu, B. Yang, P. K. Lala, and C. Peng Nodal and ALK7 Inhibit Proliferation and Induce Apoptosis in Human Trophoblast Cells J. Biol. Chem., July 23, 2004; 279(30): 31277 - 31286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-C. Kim, H. van Gelder, T. A. Kim, H.-J. Lee, K. G. Baik, H. H. Chun, D. A. Lee, K. S. Choi, and S.-J. Kim Activin Receptor-like Kinase-7 Induces Apoptosis through Activation of MAPKs in a Smad3-dependent Mechanism in Hepatoma Cells J. Biol. Chem., July 2, 2004; 279(27): 28458 - 28465. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. R. Dunn, S. D. Vincent, L. Oxburgh, E. J. Robertson, and E. K. Bikoff Combinatorial activities of Smad2 and Smad3 regulate mesoderm formation and patterning in the mouse embryo Development, April 15, 2004; 131(8): 1717 - 1728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mazerbourg, C. Klein, J. Roh, N. Kaivo-Oja, D. G. Mottershead, O. Korchynskyi, O. Ritvos, and A. J. W. Hsueh Growth Differentiation Factor-9 Signaling Is Mediated by the Type I Receptor, Activin Receptor-Like Kinase 5 Mol. Endocrinol., March 1, 2004; 18(3): 653 - 665. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. DaCosta Byfield, C. Major, N. J. Laping, and A. B. Roberts SB-505124 Is a Selective Inhibitor of Transforming Growth Factor-{beta} Type I Receptors ALK4, ALK5, and ALK7 Mol. Pharmacol., March 1, 2004; 65(3): 744 - 752. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Mathieu, K. Griffin, P. Herbomel, T. Dickmeis, U. Strahle, D. Kimelman, F. M. Rosa, and N. Peyrieras Nodal and Fgf pathways interact through a positive regulatory loop and synergize to maintain mesodermal cell populations Development, February 1, 2004; 131(3): 629 - 641. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. W. Harms and C. Chang Tomoregulin-1 (TMEFF1) inhibits nodal signaling through direct binding to the nodal coreceptor Cripto Genes & Dev., November 1, 2003; 17(21): 2624 - 2629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Parisi, D. D'Andrea, C. T. Lago, E. D. Adamson, M. G. Persico, and G. Minchiotti Nodal-dependent Cripto signaling promotes cardiomyogenesis and redirects the neural fate of embryonic stem cells J. Cell Biol., October 27, 2003; 163(2): 303 - 314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Rebbapragada, H. Benchabane, J. L. Wrana, A. J. Celeste, and L. Attisano Myostatin Signals through a Transforming Growth Factor {beta}-Like Signaling Pathway To Block Adipogenesis Mol. Cell. Biol., October 15, 2003; 23(20): 7230 - 7242. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Roberts, S. Hu, Q. Qiu, P. C.K. Leung, I. Caniggia, A. Gruslin, B. Tsang, and C. Peng Identification of Novel Isoforms of Activin Receptor-Like Kinase 7 (ALK7) Generated by Alternative Splicing and Expression of ALK7 and Its Ligand, Nodal, in Human Placenta Biol Reprod, May 1, 2003; 68(5): 1719 - 1726. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Gray, C. A. Harrison, and W. Vale Cripto forms a complex with activin and type II activin receptors and can block activin signaling PNAS, April 29, 2003; 100(9): 5193 - 5198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Schlange, H.-H. Arnold, and T. Brand BMP2 is a positive regulator of Nodal signaling during left-right axis formation in the chicken embryo Development, March 9, 2003; 129(14): 3421 - 3429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Cheng, F. Olale, J. T. Bennett, A. H. Brivanlou, and A. F. Schier EGF-CFC proteins are essential coreceptors for the TGF-beta signals Vg1 and GDF1 Genes & Dev., January 1, 2003; 17(1): 31 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. M. Rosa Cripto, a Multifunctional Partner in Signaling: Molecular Forms and Activities Sci. Signal., November 12, 2002; 2002(158): pe47 - pe47. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Oh, C.-Y. Yeo, Y. Lee, H. Schrewe, M. Whitman, and E. Li Activin type IIA and IIB receptors mediate Gdf11 signaling in axial vertebral patterning Genes & Dev., November 1, 2002; 16(21): 2749 - 2754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Valcourt, J. Gouttenoire, A. Moustakas, D. Herbage, and F. Mallein-Gerin Functions of Transforming Growth Factor-beta Family Type I Receptors and Smad Proteins in the Hypertrophic Maturation and Osteoblastic Differentiation of Chondrocytes J. Biol. Chem., September 6, 2002; 277(37): 33545 - 33558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-T. Yan, J.-J. Liu, Y. Luo, C. E, R. S. Haltiwanger, C. Abate-Shen, and M. M. Shen Dual Roles of Cripto as a Ligand and Coreceptor in the Nodal Signaling Pathway Mol. Cell. Biol., July 1, 2002; 22(13): 4439 - 4449. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Inman, F. J. Nicolas, J. F. Callahan, J. D. Harling, L. M. Gaster, A. D. Reith, N. J. Laping, and C. S. Hill 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., July 1, 2002; 62(1): 65 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Bianco, H. B. Adkins, C. Wechselberger, M. Seno, N. Normanno, A. De Luca, Y. Sun, N. Khan, N. Kenney, A. Ebert, et al. Cripto-1 Activates Nodal- and ALK4-Dependent and -Independent Signaling Pathways in Mammary Epithelial Cells Mol. Cell. Biol., April 15, 2002; 22(8): 2586 - 2597. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Ring, S. Ogata, L. Meek, J. Song, T. Ohta, K. Miyazono, and K. W.Y. Cho The role of a Williams-Beuren syndrome-associated helix-loop-helix domain-containing transcription factor in activin/nodal signaling Genes & Dev., April 1, 2002; 16(7): 820 - 835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. B. David, L. Saint-Etienne, M. Tsang, T. F. Schilling, and F. M. Rosa Requirement for endoderm and FGF3 in ventral head skeleton formation Development, January 10, 2002; 129(19): 4457 - 4468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Mathieu, A. Barth, F. M. Rosa, S. W. Wilson, and N. Peyrieras Distinct and cooperative roles for Nodal and Hedgehog signals during hypothalamic development Development, January 7, 2002; 129(13): 3055 - 3065. [Abstract] [Full Text] [PDF]
|
|
