Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.3.16 (
calcineurin
)
17,112
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The transient receptor potential (TRP; C-classical, TRPC) channel TRPC3 allows a cation (Na
+
/Ca
2+
) influx that is favored by the stimulation of G
q
protein-coupled receptors (GPCRs). An enhanced TRPC3 activity is related to adverse effects, including pathological hypertrophy in chronic cardiac disease states. In the present study, we identified FK506-binding protein 52 (
FKBP52
, also known as FKBP4) as a novel interaction partner of TRPC3 in the heart.
FKBP52
was recovered from a cardiac cDNA library by a C-terminal TRPC3 fragment (amino acids 742-848) in a yeast two-hybrid screen. Downregulation of
FKBP52
promoted a TRPC3-dependent hypertrophic response in neonatal rat cardiomyocytes (NRCs). A similar effect was achieved by overexpressing peptidyl-prolyl isomerase (PPIase)-deficient
FKBP52
mutants. Mechanistically, expression of the
FKBP52
truncation mutants elevated TRPC3-mediated currents and Ca
2+
fluxes, and the activation of
calcineurin
and the nuclear factor of activated T-cells in NRCs. Our data demonstrate that
FKBP52
associates with TRPC3 via an as-yet-undescribed binding site in the C-terminus of TRPC3 and modulates TRPC3-dependent Ca
2+
signals in a PPIase-dependent manner. This functional interaction might be crucial for limiting TRPC3-dependent signaling during chronic hypertrophic stimulation.
...
PMID:FKBP52 regulates TRPC3-dependent Ca
2+
signals and the hypertrophic growth of cardiomyocyte cultures. 3154 Sep 54
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