Linked Life Data

20074556

Source:http://linkedlifedata.com/resource/pubmed/id/20074556

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-2-17
pubmed:abstractText
Receptor activity-modifying protein 2 (RAMP2) enables calcitonin receptor-like receptor (CRLR) to form an adrenomedullin (AM)-specific receptor. Here we investigated the function of the cytoplasmic C-terminal tail (C-tail) of human (h)CRLR by co-transfecting its C-terminal mutants into HEK-293 cells stably expressing hRAMP2. Deleting the C-tail from CRLR disrupted AM-evoked cAMP production or receptor internalization, but did not affect [(125)I]AM binding. We found that CRLR residues 428-439 are required for AM-evoked cAMP production, though deleting this region had little effect on receptor internalization. Moreover, pretreatment with pertussis toxin (100ng/mL) led to significant increases in AM-induced cAMP production via wild-type CRLR/RAMP2 complexes. This effect was canceled by deleting CRLR residues 454-457, suggesting Gi couples to this region. Flow cytometric analysis revealed that CRLR truncation mutants lacking residues in the Ser/Thr-rich region extending from Ser(449) to Ser(467) were unable to undergo AM-induced receptor internalization and, in contrast to the effect on wild-type CRLR, overexpression of GPCR kinases-2, -3 and -4 failed to promote internalization of CRLR mutants lacking residues 449-467. Thus, the hCRLR C-tail is crucial for AM-evoked cAMP production and internalization of the CRLR/RAMP2, while the receptor internalization is dependent on the aforementioned GPCR kinases, but not Gs coupling.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1090-2104
pubmed:author
pubmed:issnType
Electronic
pubmed:day
12
pubmed:volume
392
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
380-5
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:20074556-Adrenomedullin, pubmed-meshheading:20074556-Amino Acid Sequence, pubmed-meshheading:20074556-Calcitonin Receptor-Like Protein, pubmed-meshheading:20074556-Cell Line, pubmed-meshheading:20074556-Cyclic AMP, pubmed-meshheading:20074556-Cytoplasm, pubmed-meshheading:20074556-Humans, pubmed-meshheading:20074556-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:20074556-Membrane Proteins, pubmed-meshheading:20074556-Molecular Sequence Data, pubmed-meshheading:20074556-Protein Structure, Tertiary, pubmed-meshheading:20074556-Receptor Activity-Modifying Protein 2, pubmed-meshheading:20074556-Receptor Activity-Modifying Proteins, pubmed-meshheading:20074556-Receptors, Calcitonin, pubmed-meshheading:20074556-Sequence Deletion, pubmed-meshheading:20074556-Transfection
pubmed:year
2010
pubmed:articleTitle
Function of the cytoplasmic tail of human calcitonin receptor-like receptor in complex with receptor activity-modifying protein 2.
pubmed:affiliation
Frontier Science Research Center, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. kuwasako@fc.miyazaki-u.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't