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PMID:17827149

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Citation

Goehring, AS, Pedroja, BS, Hinke, SA, Langeberg, LK and Scott, JD (2007) MyRIP anchors protein kinase A to the exocyst complex. J. Biol. Chem. 282:33155-67

Abstract

The movement of signal transduction enzymes in and out of multi-protein complexes coordinates the spatial and temporal resolution of cellular events. Anchoring and scaffolding proteins are key to this process because they sequester protein kinases and phosphatases with a subset of their preferred substrates. The protein kinase A-anchoring family of proteins (AKAPs), which target the cAMP-dependent protein kinase (PKA) and other enzymes to defined subcellular microenvironments, represent a well studied group of these signal-organizing molecules. In this report we demonstrate that the Rab27a GTPase effector protein MyRIP is a member of the AKAP family. The zebrafish homolog of MyRIP (Ze-AKAP2) was initially detected in a two-hybrid screen for AKAPs. A combination of biochemical, cell-based, and immunofluorescence approaches demonstrate that the mouse MyRIP ortholog targets the type II PKA holoenzyme via an atypical mechanism to a specific perinuclear region of insulin-secreting cells. Similar approaches show that MyRIP interacts with the Sec6 and Sec8 components of the exocyst complex, an evolutionarily conserved protein unit that controls protein trafficking and exocytosis. These data indicate that MyRIP functions as a scaffolding protein that links PKA to components of the exocytosis machinery.

Links

PubMed Online version:10.1074/jbc.M705167200

Keywords

A Kinase Anchor Proteins/chemistry; A Kinase Anchor Proteins/genetics; A Kinase Anchor Proteins/metabolism; Amino Acid Sequence; Animals; Binding Sites; Cell Line; Cyclic AMP-Dependent Protein Kinases/classification; Cyclic AMP-Dependent Protein Kinases/genetics; Cyclic AMP-Dependent Protein Kinases/metabolism; Humans; Mice; Molecular Sequence Data; Protein Binding; Sequence Alignment; Sequence Homology, Amino Acid; Vesicular Transport Proteins/chemistry; Vesicular Transport Proteins/genetics; Vesicular Transport Proteins/metabolism; Zebrafish; Zebrafish Proteins/chemistry; Zebrafish Proteins/genetics; Zebrafish Proteins/metabolism

Significance

Annotations

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

DANRE:MYRIP

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

ZFIN:ZDB-GENE-030131-1007

F

Seeded From UniProt

complete

DANRE:A9C3T0

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

ZFIN:ZDB-GENE-080123-1

F

Seeded From UniProt

complete

MOUSE:KAP2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8NFW9

F

Seeded From UniProt

complete

MOUSE:KAP2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8K3I4

F

Seeded From UniProt

complete

DANRE:Q08BH1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

ZFIN:ZDB-GENE-080123-1

F

Seeded From UniProt

complete

RAT:EXOC4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8K3I4

F

Seeded From UniProt

complete

RAT:EXOC3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8K3I4

F

Seeded From UniProt

complete

RAT:MYRIP

located_in

GO:0048471: perinuclear region of cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:MYRIP

involved_in

GO:0032024: positive regulation of insulin secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:MYRIP

located_in

GO:0031045: dense core granule

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:MYRIP

enables

GO:0051018: protein kinase A binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:MYRIP

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q62824

F

Seeded From UniProt

complete

MOUSE:MYRIP

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q62825

F

Seeded From UniProt

complete

MOUSE:MYRIP

part_of

GO:0000145: exocyst

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:MYRIP

enables

GO:0051018: protein kinase A binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P12367

F

Seeded From UniProt

complete

HUMAN:MYRIP

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P12367

F

Seeded From UniProt

complete

See also

References

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