Linked Life Data

11007779

Source:http://linkedlifedata.com/resource/pubmed/id/11007779

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
52
pubmed:dateCreated
2001-1-25
pubmed:abstractText
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: Ca(2+)/calmodulin, receptor tyrosine kinase, and TGF-beta pathways.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
41430-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11007779-Amino Acid Sequence, pubmed-meshheading:11007779-Animals, pubmed-meshheading:11007779-Base Sequence, pubmed-meshheading:11007779-Binding Sites, pubmed-meshheading:11007779-Calmodulin, pubmed-meshheading:11007779-DNA-Binding Proteins, pubmed-meshheading:11007779-Female, pubmed-meshheading:11007779-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:11007779-Molecular Sequence Data, pubmed-meshheading:11007779-Morphogenesis, pubmed-meshheading:11007779-Myosins, pubmed-meshheading:11007779-Phosphorylation, pubmed-meshheading:11007779-Smad Proteins, pubmed-meshheading:11007779-Smad2 Protein, pubmed-meshheading:11007779-Structure-Activity Relationship, pubmed-meshheading:11007779-Trans-Activators, pubmed-meshheading:11007779-Xenopus, pubmed-meshheading:11007779-Xenopus Proteins
pubmed:year
2000
pubmed:articleTitle
Calmodulin differentially modulates Smad1 and Smad2 signaling.
pubmed:affiliation
Center for Developmental Biology, Department of Molecular Biology and Oncology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9133, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't