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PMID:20054002

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Citation

Ouchi, N, Asaumi, Y, Ohashi, K, Higuchi, A, Sono-Romanelli, S, Oshima, Y and Walsh, K (2010) DIP2A functions as a FSTL1 receptor. J. Biol. Chem. 285:7127-34

Abstract

FSTL1 is an extracellular glycoprotein whose functional significance in physiological and pathological processes is incompletely understood. Recently, we have shown that FSTL1 acts as a muscle-derived secreted factor that is up-regulated by Akt activation and ischemic stress and that FSTL1 exerts favorable actions on the heart and vasculature. Here, we sought to identify the receptor that mediates the cellular actions of FSTL1. We identified DIP2A as a novel FSTL1-binding partner from the membrane fraction of endothelial cells. Co-immunoprecipitation assays revealed a direct physical interaction between FSTL1 and DIP2A. DIP2A was present on the cell surface of endothelial cells, and knockdown of DIP2A by small interfering RNA reduced the binding of FSTL1 to cells. In cultured endothelial cells, knockdown of DIP2A by small interfering RNA diminished FSTL1-stimulated survival, migration, and differentiation into network structures and inhibited FSTL1-induced Akt phosphorylation. In cultured cardiac myocytes, ablation of DIP2A reduced the protective actions of FSTL1 on hypoxia/reoxygenation-induced apoptosis and suppressed FSTL1-induced Akt phosphorylation. These data indicate that DIP2A functions as a novel receptor that mediates the cardiovascular protective effects of FSTL1.

Links

PubMed PMC2844162 Online version:10.1074/jbc.M109.069468

Keywords

Animals; Apoptosis/physiology; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cell Differentiation/physiology; Cell Movement/physiology; Cells, Cultured; Endothelial Cells/cytology; Endothelial Cells/physiology; Follistatin-Related Proteins/genetics; Follistatin-Related Proteins/metabolism; Humans; Mice; Myocytes, Cardiac/cytology; Myocytes, Cardiac/physiology; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Proto-Oncogene Proteins c-akt/genetics; Proto-Oncogene Proteins c-akt/metabolism; RNA, Small Interfering/genetics; RNA, Small Interfering/metabolism; Rats; Signal Transduction/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:DIP2A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q62356

F

Seeded From UniProt

complete

HUMAN:DIP2A

located_in

GO:0016020: membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:DIP2A

located_in

GO:0009986: cell surface

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FSTL1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q14689

F

Seeded From UniProt

complete

MOUSE:FSTL1

involved_in

GO:0045446: endothelial cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FSTL1

involved_in

GO:0043542: endothelial cell migration

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FSTL1

involved_in

GO:0043542: endothelial cell migration

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FSTL1

involved_in

GO:0043066: negative regulation of apoptotic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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