scholarly journals In smooth muscle, FK506-binding protein modulates IP3 receptor-evoked Ca2+ release by mTOR and calcineurin

2005 ◽  
Vol 118 (23) ◽  
pp. 5443-5451 ◽  
Author(s):  
D. MacMillan
Keyword(s):  
Smooth Muscle ◽  
Binding Protein ◽  
Ip3 Receptor ◽  
Fk506 Binding Protein

Characterization and mapping of the 12kDa FK506-binding protein (FKBP12)-binding site on different isoforms of the ryanodine receptor and of the inositol 1,4,5-trisphosphate receptor

2001 ◽  
Vol 354 (2) ◽  
pp. 413-422 ◽  
Author(s):  
Geert BULTYNCK ◽  
Patrick DE SMET ◽  
Daniela ROSSI ◽  
Geert CALLEWAERT ◽  
Ludwig MISSIAEN ◽  
...  
Keyword(s):  
Binding Site ◽  
Ryanodine Receptor ◽  
Binding Protein ◽  
Limited Proteolysis ◽  
Ip3 Receptor ◽  
Fk506 Binding Protein ◽  
High Affinity ◽  
Receptor Isoforms ◽  
Inositol 1,4,5 Trisphosphate ◽  
Affinity Interaction

We investigated the interaction of the 12kDa FK506-binding protein (FKBP12) with two ryanodine-receptor isoforms (RyR1 and RyR3) and with two myo-inositol 1,4,5-trisphosphate (IP3) receptor isoforms (IP3R1 and IP3R3). Using glutathione S-transferase (GST)-FKBP12 affinity chromatography, we could efficiently extract RyR1 (42±7% of the solubilized RyR1) from terminal cisternae of skeletal muscle as well as RyR3 (32±4% of the solubilized RyR3) from RyR3-overexpressing HEK-293 cells. These interactions were completely abolished by FK506 (20µM) but were largely unaffected by RyR-channel modulators. In contrast, neither IP3R1 nor IP3R3 from various sources, including rabbit cerebellum, A7r5 smooth-muscle cells and IP3R-overexpressing Sf9 insect cells from Spodoptera frugiperda, were retained on the GST-FKBP12 matrix. Moreover, immunoprecipitation experiments indicated a high-affinity interaction of FKBP12 with RyR1 but not with IP3R1. In order to determine the FKBP12-binding site, we fragmented both RyR1 and IP3R1 by limited proteolysis. We obtained a 45kDa fragment of RyR1 that bound to the GST-FKBP12 matrix, indicating that it retained all requirements for FKBP12 binding. This fragment was identified by its interaction with antibody m34C and must therefore contain its epitope (amino acids 2756–2803). However, no fragment of IP3R1 was retained on the column. These molecular data are in agreement with the lack of correlation between FKBP12 and IP3R1 expression in various cell types. The observation that FKBP12 did not affect IP3-induced Ca2+ release but reduced caffeine-induced Ca2+ release also indicated that mature IP3R1 and IP3R3, in contrast to RyR1 and RyR3, did not display a specific, high-affinity interaction with FKBP12.

Autoantibodies to FK506 Binding Protein 12 (FKBP12) in Autoimmune Diseases

Autoimmunity ◽  
1999 ◽  
Vol 29 (3) ◽  
pp. 159-170 ◽  
Author(s):  
Nobuhiko Shinkura ◽  
Iwao Ikai ◽  
Akira Yamauchl ◽  
Tetsuro Hirose ◽  
Yasuhiro Kawap ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Binding Protein ◽  
Fk506 Binding Protein

scholarly journals FK506-binding protein 5 promotes the progression of papillary thyroid carcinoma

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110083
Author(s):  
Zhenya Gao ◽  
Fang Yu ◽  
Huanxia Jia ◽  
Zhuo Ye ◽  
Shijie Yao
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Binding Protein ◽  
Progression Free Survival ◽  
Papillary Thyroid ◽  
Expression Levels ◽  
Fk506 Binding Protein ◽  
Normal Tissues ◽  
Induced Apoptosis

Objective To detect the expression of FK506-binding protein 5 (FKBP5) in human papillary thyroid carcinoma (PTC) tissues, and explore its possible role in the progression of PTC. Methods FKBP5 expression levels were assessed in 115 PTC tissues and corresponding normal tissues by immunohistochemistry. We also examined the correlations between FKBP5 expression and clinicopathological factors and survival in 75 patients with PTC. The effects of FKBP5 on the proliferation and apoptosis of PTC cells were detected by colony-formation, MTT, and flow cytometry assays, respectively. We further investigated the effects of FKBP5 on tumor growth in mice. Results We revealed high expression levels of FKBP5 in human PTC tissues compared with normal tissues. Furthermore, high FKBP5 expression was associated with an increased incidence of intraglandular dissemination, and lower overall and progression-free survival. FKBP5 depletion remarkably suppressed the proliferation and induced apoptosis of PTC cells in vitro. FKBP5 further contributed to the growth of PTC tumors in mice. Conclusions The results of this study demonstrated the potential involvement of FKBP5 in the progression of PTC, and confirmed FKBP5 as a novel therapeutic target for PTC treatment.

scholarly journals Disrupting Function of FK506-Binding Protein 1b/12.6 Induces the Ca2+-Dysregulation Aging Phenotype in Hippocampal Neurons

2011 ◽  
Vol 31 (5) ◽  
pp. 1693-1703 ◽  
Author(s):  
J. C. Gant ◽  
K.-C. Chen ◽  
C. M. Norris ◽  
I. Kadish ◽  
O. Thibault ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Binding Protein ◽  
Fk506 Binding Protein

scholarly journals Sex-related effects on diabetes-induced alterations in calcium release in the rat heart

2007 ◽  
Vol 293 (6) ◽  
pp. H3584-H3592 ◽  
Author(s):  
Nazmi Yaras ◽  
Erkan Tuncay ◽  
Nuhan Purali ◽  
Babur Sahinoglu ◽  
Guy Vassort ◽  
...  
Keyword(s):  
Calcium Release ◽  
Binding Protein ◽  
Ryanodine Receptors ◽  
Left Ventricular ◽  
Adult Rats ◽  
Fk506 Binding Protein ◽  
Pressure Development ◽  
Spatiotemporal Parameters ◽  
Intracellular Ca ◽  
Developed Pressure

The present study was designed to determine whether the properties of local Ca2+ release and its related regulatory mechanisms might provide insight into the role of sex differences in heart functions of control and streptozotocin-induced diabetic adult rats. Left ventricular developed pressure, the rates of pressure development and decay (±dP/d t), basal intracellular Ca2+ level ([Ca2+]i), and spatiotemporal parameters of [Ca2+]i transients were found to be similar in male and female control rats. However, spatiotemporal parameters of Ca2+ sparks in cardiomyocytes isolated from control females were significantly larger and slower than those in control males. Diabetes reduced left ventricular developed pressure to a lower extent in females than in males, and the diabetes-induced depressions in both +dP/d t and −dP/d t were less in females than in males. Diabetes elicited a smaller reduction in the amplitude of [Ca2+]i transients in females than in males, a smaller reduction in sarcoplasmic reticulum-Ca2+ load, and less increase in basal [Ca2+]i. Similarly, the elementary Ca2+ events and their control proteins were clearly different in both sexes, and these differences were more marked in diabetes. Diabetes-induced depression of the Ca2+ spark amplitude was significantly less in females than in matched males. Levels of cardiac ryanodine receptors (RyR2) and FK506-binding protein 12.6 in control females were significantly higher than those shown in control males. Diabetes induced less RyR2 phosphorylation and FK506-binding protein 12.6 unbinding in females. Moreover, total and free sulfhydryl groups were significantly less reduced, and PKC levels were less increased, in diabetic females than in diabetic males. The present data related to local Ca2+ release and its related proteins describe some of the mechanisms that may underlie sex-related differences accounting for females to have less frequent development of cardiac diseases.

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