GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:21262972

From GONUTS
Jump to: navigation, search
Citation

Chen, H, Liu, L, Ma, B, Ma, TM, Hou, JJ, Xie, GM, Wu, W, Yang, FQ and Chen, YG (2011) Protein kinase A-mediated 14-3-3 association impedes human Dapper1 to promote dishevelled degradation. J. Biol. Chem. 286:14870-80

Abstract

Wnt signaling regulates embryo development and tissue homeostasis, and its deregulation leads to an array of diseases, including cancer. Dapper1 has been shown to be a key negative regulator of Wnt signaling. However, its function and regulation remain poorly understood. In this study, we report that 14-3-3β interacts with human Dapper1 (hDpr1). The interaction is dependent on protein kinase A (PKA)-mediated phosphorylation of hDpr1 at Ser-237 and Ser-827. 14-3-3β binding attenuates the ability of hDpr1 to promote Dishevelled (Dvl) degradation, thus enhancing Wnt signaling. We further provide evidence that PKA-mediated Dpr1 phosphorylation may contribute to growth and tumor formation of colon cancer Caco2 cells. Finally, we show that cyclooxygenase-2 expression and PKA activation are positively correlated with Dvl protein levels in colon cancer samples. Together, our findings establish a novel layer of regulation of Wnt signaling by PKA via the 14-3-3-Dpr1-Dvl axis.

Links

PubMed PMC3083226 Online version:10.1074/jbc.M110.211607

Keywords

14-3-3 Proteins/metabolism; Adaptor Proteins, Signal Transducing/antagonists & inhibitors; Adaptor Proteins, Signal Transducing/metabolism; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms/pathology; Cyclic AMP-Dependent Protein Kinases/metabolism; Humans; Nuclear Proteins/antagonists & inhibitors; Phosphoproteins/metabolism; Phosphorylation; Protein Binding/physiology; Wnt Proteins/metabolism

Significance

Annotations

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

HUMAN:DVL2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9NYF0

F

Seeded From UniProt

complete

HUMAN:1433B

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9NYF0

F

Seeded From UniProt

complete

HUMAN:DACT1

involved_in

GO:0030177: positive regulation of Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:DACT1

involved_in

GO:0031647: regulation of protein stability

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:DACT1

enables

GO:0051018: protein kinase A binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:DACT1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O14641

F

Seeded From UniProt

complete

HUMAN:DACT1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P31946

F

Seeded From UniProt

complete

See also

References

See Help:References for how to manage references in GONUTS.