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PMID: 9865696 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

SARA, a FYVE domain protein that recruits Smad2 to the TGFbeta receptor.

Cell ·Vol. 95 ·No. 6 ·1998-12-11 ·Pages 779-91

Tsukazaki T, Chiang TA, Davison AF, Attisano L, Wrana JL

Abstract

Smads transmit signals from transmembrane ser/thr kinase receptors to the nucleus. We now identify SARA (for Smad anchor for receptor activation), a FYVE domain protein that interacts directly with Smad2 and Smad3. SARA functions to recruit Smad2 to the TGFbeta receptor by controlling the subcellular localization of Smad2 and by interacting with the TGFbeta receptor complex. Phosphorylation of Smad2 induces dissociation from SARA with concomitant formation of Smad2/Smad4 complexes and nuclear translocation. Furthermore, mutations in SARA that cause mislocalization of Smad2 inhibit TGFbeta-dependent transcriptional responses, indicating that the regulation of Smad localization is important for TGFbeta signaling. These results thus define SARA as a component of the TGFbeta pathway that brings the Smad substrate to the receptor.

MeSH Terms

3T3 Cells Adult Amino Acid Sequence Animals Binding Sites COS Cells Carrier Proteins/genetics,metabolism DNA-Binding Proteins/metabolism Humans Intracellular Signaling Peptides and Proteins Mice Molecular Sequence Data Nerve Growth Factors Phosphorylation Protein Serine-Threonine Kinases Rabbits Receptor, Transforming Growth Factor-beta Type II Receptors, Transforming Growth Factor beta/metabolism Recombinant Fusion Proteins/metabolism Serine Endopeptidases Signal Transduction Smad Proteins Smad2 Protein Smad3 Protein Smad4 Protein Subcellular Fractions Trans-Activators/metabolism Transforming Growth Factor beta/metabolism Tumor Cells, Cultured Xenopus Xenopus Proteins Zinc Fingers

Chemicals

Carrier Proteins DNA-Binding Proteins Intracellular Signaling Peptides and Proteins Nerve Growth Factors Receptors, Transforming Growth Factor beta Recombinant Fusion Proteins SMAD2 protein, human SMAD3 protein, human SMAD4 protein, human Smad Proteins Smad2 Protein Smad2 protein, Xenopus Smad2 protein, mouse Smad3 Protein Smad3 protein, mouse Smad4 Protein Smad4 protein, mouse Trans-Activators Transforming Growth Factor beta Xenopus Proteins ZFYVE9 protein, Xenopus madh3 protein, Xenopus smad4.1 protein, Xenopus smad4.2 protein, Xenopus Protein Serine-Threonine Kinases Receptor, Transforming Growth Factor-beta Type II ZFYVE16 protein, human Serine Endopeptidases

Authors & Affiliations

5 authors, click to expand affiliations / ORCID

Tsukazaki T

Program in Developmental Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.

Chiang T A

Davison A F

Attisano L

Wrana J L

Article Info

Journal

Cell

Abbr.

Cell

ISSN

0092-8674

DOI

10.1016/s0092-8674(00)81701-8

Published

1998-12-11

Pages

779-91

Language

English

Region

United States

NLM ID

0413066

Subset

Databases

GENBANK

AF104304, AF104305

External Links

PubMed source DOI: 10.1016/s0092-8674(00)81701-8 View journal details

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SARA, a FYVE domain protein that recruits Smad2 to the TGFbeta receptor.

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