Immunophilin FK506 binding protein associated with inositol 1,4,5-trisphosphate receptor modulates calcium flux.

0301 basic medicine 0303 health sciences Muscle Proteins Receptors, Cytoplasmic and Nuclear Ryanodine Receptor Calcium Release Channel Inositol 1,4,5-Trisphosphate Polyenes In Vitro Techniques Endoplasmic Reticulum Recombinant Proteins Cell Compartmentation Rats 3. Good health DNA-Binding Proteins 03 medical and health sciences Cerebellum Cyclosporine Animals Inositol 1,4,5-Trisphosphate Receptors Calcium Channels Carrier Proteins Ion Channel Gating Heat-Shock Proteins Protein Binding
DOI: 10.1073/pnas.92.5.1784 Publication Date: 2006-05-31T13:27:59Z
ABSTRACT
The immunophilin FK506 binding protein 12 (FKBP12) is associated with and modulates the ryanodine receptor calcium release channel of skeletal muscle. Ryanodine receptor has amino acid homology and functional similarity with another intracellular Ca2+ release channel, the inositol 1,4,5-trisphosphate receptor (IP3R). In the present study we show that highly purified preparations of IP3R contain FKBP12. The complex of these two proteins is disrupted by the immunosuppressants FK506 and rapamycin, both of which are known to bind FKBP12 with high affinity. Disrupting the IP3R-FKBP12 interaction increases Ca2+ flux through IP3R, an effect that is reversed by added FKBP12. FKBP12 appears to be physiologically linked to IP3R, regulating its Ca2+ conductance.
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