RGD Reference Report - Cyclic ADP-ribose binds to FK506-binding protein 12.6 to release Ca2+ from islet microsomes. - Rat Genome Database

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Cyclic ADP-ribose binds to FK506-binding protein 12.6 to release Ca2+ from islet microsomes.

Authors: Noguchi, N  Takasawa, S  Nata, K  Tohgo, A  Kato, I  Ikehata, F  Yonekura, H  Okamoto, H 
Citation: Noguchi N, etal., J Biol Chem 1997 Feb 7;272(6):3133-6.
RGD ID: 61587
Pubmed: PMID:9013543   (View Abstract at PubMed)

Cyclic ADP-ribose (cADPR) is a second messenger for Ca2+ mobilization via the ryanodine receptor (RyR) from islet microsomes for insulin secretion (Takasawa, S., Nata, K., Yonekura, H., and Okamoto, H. (1993) Science 259, 370-373). In the present study, FK506, an immunosuppressant that prolongs allograft survival, as well as cADPR were found to induce the release of Ca2+ from islet microsomes. After islet microsomes were treated with FK506, the Ca2+ release by cADPR from microsomes was reduced. cADPR as well as FK506 bound to FK506-binding protein 12.6 (FKBP12.6), which we also found occurs naturally in islet microsomes. When islet microsomes were treated with cADPR, FKBP12.6 dissociated from the microsomes and moved to the supernatant, releasing Ca2+ from the intracellular stores. The microsomes that were then devoid of FKBP12.6 did not show Ca2+ release by cADPR. These results strongly suggest that cADPR may be the ligand for FKBP12.6 in islet RyR and that the binding of cADPR to FKBP12.6 frees the RyR from FKBP12.6, causing it to release Ca2+.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of cytosolic calcium ion concentration  IDA 61587 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cyclic nucleotide binding  IDA 61587 RGD 
FK506 binding  IDA 61587; 61587 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Fkbp1a  (FKBP prolyl isomerase 1A)
Fkbp1b  (FKBP prolyl isomerase 1B)


Additional Information