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:19139280

From GONUTS
Jump to: navigation, search
Citation

Ding, J and Du, K (2009) ClipR-59 interacts with Akt and regulates Akt cellular compartmentalization. Mol. Cell. Biol. 29:1459-71

Abstract

Akt is activated on the plasma membrane and its substrates are distributed throughout various cellular compartments. To phosphorylate its substrates, Akt needs to be recruited to specific intracellular compartments. Thus, regulation of Akt cellular compartmentalization constitutes an important mechanism to specify Akt signaling. Here, we report the identification of ClipR-59 as an Akt interaction protein. We show that the interaction of ClipR-59 with Akt is mediated by the CAP-Gly domain of ClipR-59 and kinase domain of Akt and is regulated by Akt phosphorylation. We demonstrate that ClipR-59 regulates the Akt membrane association through its interaction with Akt and membrane localization and, by modulating Akt cellular compartmentalization, differentially modulates phosphorylation of Akt substrates in adipocytes. Finally, we provide evidence that one of the Akt substrates whose phosphorylation is upregulated by ClipR-59 is AS160, a negative regulator of adipocyte glucose transport. Accordingly, ectopic expression of ClipR-59 enhances, whereas knockdown of ClipR-59 suppresses, adipocyte glucose transport. We suggest that ClipR-59 functions as a scaffold protein that interacts with phospho-Akt and recruits active Akt on the membrane and may play an important role in adipocyte glucose transport.

Links

PubMed PMC2648236 Online version:10.1128/MCB.00754-08

Keywords

Adipocytes/physiology; Animals; Biological Transport; Cell Compartmentation/physiology; Cell Line; Cell Membrane/metabolism; GTPase-Activating Proteins/metabolism; Glucose/metabolism; Humans; Mice; Microtubule-Associated Proteins/metabolism; Phosphorylation; Protein Binding; Proto-Oncogene Proteins c-akt/metabolism; Up-Regulation/physiology

Significance

Annotations

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

MOUSE:CLIP3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q60823

F

Seeded From UniProt

complete

MOUSE:CLIP3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P31750

F

Seeded From UniProt

complete

MOUSE:CLIP3

involved_in

GO:0001934: positive regulation of protein phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CLIP3

located_in

GO:0005802: trans-Golgi network

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CLIP3

involved_in

GO:0010828: positive regulation of glucose transmembrane transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CLIP3

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CLIP3

involved_in

GO:0045444: fat cell differentiation

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CLIP3

involved_in

GO:1903078: positive regulation of protein localization to plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:AKT1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:B9EHT4

F

Seeded From UniProt

complete

MOUSE:AKT2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:B9EHT4

F

Seeded From UniProt

complete

HUMAN:CLIP3

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:AKT1

involved_in

GO:0032869: cellular response to insulin stimulus

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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