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PMID:9620797

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Citation

McLatchie, LM, Fraser, NJ, Main, MJ, Wise, A, Brown, J, Thompson, N, Solari, R, Lee, MG and Foord, SM (1998) RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 393:333-9

Abstract

Calcitonin-gene-related peptide (CGRP) and adrenomedullin are related peptides with distinct pharmacological profiles. Here we show that a receptor with seven transmembrane domains, the calcitonin-receptor-like receptor (CRLR), can function as either a CGRP receptor or an adrenomedullin receptor, depending on which members of a new family of single-transmembrane-domain proteins, which we have called receptor-activity-modifying proteins or RAMPs, are expressed. RAMPs are required to transport CRLR to the plasma membrane. RAMP1 presents the receptor at the cell surface as a mature glycoprotein and a CGRP receptor. RAMP2-transported receptors are core-glycosylated and are adrenomedullin receptors.

Links

PubMed Online version:10.1038/30666

Keywords

3T3 Cells; Adrenomedullin; Amino Acid Sequence; Animals; Biological Transport; Calcitonin/chemistry; Calcitonin/metabolism; Calcitonin Gene-Related Peptide/genetics; Calcitonin Gene-Related Peptide/metabolism; Calcitonin Receptor-Like Protein; Cell Line; Cloning, Molecular; Cross-Linking Reagents; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism; Gene Expression; Glycosylation; Humans; Intracellular Signaling Peptides and Proteins; Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase/metabolism; Membrane Proteins/genetics; Membrane Proteins/metabolism; Mice; Molecular Sequence Data; Peptides/metabolism; RNA, Messenger/metabolism; Receptor Activity-Modifying Protein 1; Receptor Activity-Modifying Protein 2; Receptor Activity-Modifying Proteins; Receptors, Adrenomedullin; Receptors, Calcitonin/metabolism; Receptors, Calcitonin Gene-Related Peptide/genetics; Receptors, Calcitonin Gene-Related Peptide/metabolism; Receptors, Peptide; Sequence Alignment; Tumor Cells, Cultured; Xenopus

Significance

Annotations

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

HUMAN:RAMP1

located_in

GO:0005887: integral component of plasma membrane

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

HUMAN:RAMP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P06881

F

Seeded From UniProt

complete

HUMAN:RAMP1

part_of

GO:1990406: CGRP receptor complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:RAMP1

involved_in

GO:0007189: adenylate cyclase-activating G protein-coupled receptor signaling pathway

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q16602

P

Seeded From UniProt

complete

HUMAN:RAMP1

enables

GO:0001635: calcitonin gene-related peptide receptor activity

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q16602

F

Seeded From UniProt

complete

HUMAN:RAMP1

colocalizes_with

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:RAMP1

enables

GO:1990407: calcitonin gene-related peptide binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q16602

F

Seeded From UniProt

complete

HUMAN:RAMP1

involved_in

GO:0060050: positive regulation of protein glycosylation

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:Q16602)

Seeded From UniProt

complete

HUMAN:RAMP1

involved_in

GO:1990408: calcitonin gene-related peptide receptor signaling pathway

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q16602

P

Seeded From UniProt

complete

HUMAN:RAMP2

located_in

GO:0005887: integral component of plasma membrane

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

HUMAN:RAMP2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P43145

F

Seeded From UniProt

complete

HUMAN:RAMP2

part_of

GO:1903143: adrenomedullin receptor complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:RAMP2

involved_in

GO:0007189: adenylate cyclase-activating G protein-coupled receptor signaling pathway

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q16602

P

Seeded From UniProt

complete

HUMAN:RAMP2

involved_in

GO:0015031: protein transport

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:RAMP2

enables

GO:0001605: adrenomedullin receptor activity

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q16602

F

Seeded From UniProt

complete

HUMAN:RAMP2

colocalizes_with

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:RAMP2

involved_in

GO:1990410: adrenomedullin receptor signaling pathway

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q16602

P

Seeded From UniProt

complete

HUMAN:RAMP3

located_in

GO:0005887: integral component of plasma membrane

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

HUMAN:RAMP3

involved_in

GO:0015031: protein transport

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:RAMP3

colocalizes_with

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CALCA

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O60894

F

Seeded From UniProt

complete

RAT:ADML

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O60895

F

Seeded From UniProt

complete

HUMAN:CALRL

part_of

GO:1903143: adrenomedullin receptor complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CALRL

part_of

GO:1990406: CGRP receptor complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CALRL

involved_in

GO:0007189: adenylate cyclase-activating G protein-coupled receptor signaling pathway

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O60894

P

Seeded From UniProt

complete

HUMAN:CALRL

involved_in

GO:0007189: adenylate cyclase-activating G protein-coupled receptor signaling pathway

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O60895

P

Seeded From UniProt

complete

HUMAN:CALRL

involved_in

GO:0015031: protein transport

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CALRL

enables

GO:0001605: adrenomedullin receptor activity

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O60895

F

Seeded From UniProt

complete

HUMAN:CALRL

enables

GO:0001635: calcitonin gene-related peptide receptor activity

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O60894

F

Seeded From UniProt

complete

HUMAN:CALRL

colocalizes_with

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CALRL

involved_in

GO:1990410: adrenomedullin receptor signaling pathway

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O60895

P

Seeded From UniProt

complete

HUMAN:CALRL

involved_in

GO:1990408: calcitonin gene-related peptide receptor signaling pathway

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O60894

P

Seeded From UniProt

complete


See also

References

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