JBC Avanti Polar Lipids

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M005727200 on September 27, 2000

J. Biol. Chem., Vol. 275, Issue 52, 41430-41438, December 29, 2000
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
275/52/41430    most recent
M005727200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Scherer, A.
Right arrow Articles by Graff, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Scherer, A.
Right arrow Articles by Graff, J. M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Calmodulin Differentially Modulates Smad1 and Smad2 Signaling*

Andreas SchererDagger and Jonathan M. Graff§

From the Center for Developmental Biology, Department of Molecular Biology and Oncology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9133

The members of the Smad protein family are intracellular mediators of transforming growth factor beta  (TGF-beta ) signaling. Smad1 transduces bone morphogenetic protein signals, inducing formation of ventral mesoderm in Xenopus embryos, whereas Smad2 transduces activin/TGF-beta signals, generating dorsal mesoderm. Calmodulin directly binds to many Smads and was shown to down-regulate Smad2 activity in a cell culture system (Zimmerman, C. M., Kariapper, M. S. T., and Mathews, L. S. (1997) J. Biol. Chem. 273, 677-680). Here, we extend those data and demonstrate that calmodulin alters Smad signaling in living embryos, increasing Smad1 activity while inhibiting Smad2 function. To characterize this regulation, we undertook a structure-function analysis and found that calmodulin binds to two distinct and conserved regions in both Smad1 and Smad2. Receptor tyrosine kinase signaling also modifies Smad activity (Kretzschmar, M., Doody, J., and Massagué, J. (1997) Nature 389, 618-622; Kretzschmar, M., Doody, J., Timokhina, I., and Massagué, J. (1999) Genes Dev. 13, 804-816; de Caestecker, M. P., Parks, W. T., Frank, C. J., Castagnino, P., Bottaro, D. P., Roberts, A. B., and Lechleider, R. J. (1998) Genes Dev. 12, 1587-1592). We show that calmodulin binding to Smads inhibits subsequent Erk2-dependent phosphorylation of Smads and vice versa. These observations suggest the presence of a cross-talk between three major signaling cascades as follows: Ca2+/calmodulin, receptor tyrosine kinase, and TGF-beta pathways.

* This work was supported in part by NICHD Grant RO1-HD36001-01A1 from the National Institutes of Health and a grant from the March of Dimes (to J. M. G.).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.

Dagger Current address: Novartis Pharma AG, WSJ 386.607, CH-4002 Basel, Switzerland. E-mail: Andreas.Scherer@Pharma.Novartis.com.

§ A Charles E. Culpeper Medical Scholar and recipient of support from the Rockefeller Brothers Fund. To whom correspondence should be addressed: Center for Developmental Biology, Dept. of Molecular Biology and Oncology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., NB 5.118A, Dallas, TX 75390-9133. Tel.: 214-648-1481; Fax: 214-648-1960; E-mail: graff02@swvx12.swmed.edu.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Dent. Res.Home page
L. Hakkinen and A. Csiszar
Hereditary Gingival Fibromatosis: Characteristics and Novel Putative Pathogenic Mechanisms
J. Dent. Res., January 1, 2007; 86(1): 25 - 34.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
G. Euler-Taimor and J. Heger
The complex pattern of SMAD signaling in the cardiovascular system
Cardiovasc Res, January 1, 2006; 69(1): 15 - 25.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
M. A. Griffin, H. Feng, M. Tewari, P. Acosta, M. Kawana, H. L. Sweeney, and D. E. Discher
{gamma}-Sarcoglycan deficiency increases cell contractility, apoptosis and MAPK pathway activation but does not affect adhesion
J. Cell Sci., April 1, 2005; 118(7): 1405 - 1416.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. ProteomicsHome page
M. Knuesel, Y. Wan, Z. Xiao, E. Holinger, N. Lowe, W. Wang, and X. Liu
Identification of Novel Protein-Protein Interactions Using A Versatile Mammalian Tandem Affinity Purification Expression System
Mol. Cell. Proteomics, November 1, 2003; 2(11): 1225 - 1233.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
X. Luo, J. Xu, and N. Chegini
The Expression of Smads in Human Endometrium and Regulation and Induction in Endometrial Epithelial and Stromal Cells by Transforming Growth Factor-{beta}
J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4967 - 4976.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
M. J. Walters, G. A. Wayman, J. C. Notis, R. H. Goodman, T. R. Soderling, and J. L. Christian
Calmodulin-dependent protein kinase IV mediated antagonism of BMP signaling regulates lineage and survival of hematopoietic progenitors
Development, March 5, 2003; 129(6): 1455 - 1466.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
J. Xu, X. Luo, and N. Chegini
Differential Expression, Regulation, and Induction of Smads, Transforming Growth Factor-{beta} Signal Transduction Pathway in Leiomyoma, and Myometrial Smooth Muscle Cells and Alteration by Gonadotropin-Releasing Hormone Analog
J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1350 - 1361.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. L. Vivian, Y. Chen, D. Yee, E. Schneider, and T. Magnuson
An allelic series of mutations in Smad2 and Smad4 identified in a genotype-based screen of N-ethyl-N- nitrosourea-mutagenized mouse embryonic stem cells
PNAS, November 26, 2002; 99(24): 15542 - 15547.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Funaba, C. M. Zimmerman, and L. S. Mathews
Modulation of Smad2-mediated Signaling by Extracellular Signal-regulated Kinase
J. Biol. Chem., October 25, 2002; 277(44): 41361 - 41368.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
C. Welt, Y. Sidis, H. Keutmann, and A. Schneyer
Activins, Inhibins, and Follistatins: From Endocrinology to Signaling. A Paradigm for the New Millennium
Experimental Biology and Medicine, October 1, 2002; 227(9): 724 - 752.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
Y.-G. Chen, H. M. Lui, S.-L. Lin, J. M. Lee, and S.-Y. Ying
Regulation of Cell Proliferation, Apoptosis, and Carcinogenesis by Activin
Experimental Biology and Medicine, February 1, 2002; 227(2): 75 - 87.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
M. W. Geraci, M. Moore, T. Gesell, M. E. Yeager, L. Alger, H. Golpon, B. Gao, J. E. Loyd, R. M. Tuder, and N. F. Voelkel
Gene Expression Patterns in the Lungs of Patients With Primary Pulmonary Hypertension : A Gene Microarray Analysis
Circ. Res., March 30, 2001; 88(6): 555 - 562.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
T. A. McGowan, M. Madesh, Y. Zhu, L. Wang, M. Russo, L. Deelman, R. Henning, S. Joseph, G. Hajnoczky, and K. Sharma
TGF-beta -induced Ca2+ influx involves the type III IP3 receptor and regulates actin cytoskeleton
Am J Physiol Renal Physiol, May 1, 2002; 282(5): F910 - F920.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.