Protein tyrosine phosphatase 1B is a mediator of cyclic ADP ribose-induced Ca²⁺ signaling in ventricular myocytes.
- Author:
Seon Ah PARK
1
;
Bing Zhe HONG
;
Ki Chan HA
;
Uh Hyun KIM
;
Myung Kwan HAN
;
Yong Geun KWAK
Author Information
- Publication Type:Original Article
- MeSH: Action Potentials; Adenosine Diphosphate*; Adenosine Triphosphatases; Calcium; Cyclic ADP-Ribose; Cytochalasin B; Endoplasmic Reticulum; Homeostasis; Muscle Cells*; Myocytes, Cardiac; Protein Tyrosine Phosphatase, Non-Receptor Type 1*; Protein Tyrosine Phosphatases*; Reticulum; Ryanodine Receptor Calcium Release Channel; Tyrosine
- From:Experimental & Molecular Medicine 2017;49(6):e341-
- CountryRepublic of Korea
- Language:English
- Abstract: Cyclic ADP-ribose (cADPR) releases Ca²⁺ from ryanodine receptor (RyR)-sensitive calcium pools in various cell types. In cardiac myocytes, the physiological levels of cADPR transiently increase the amplitude and frequency of Ca²⁺ (that is, a rapid increase and decrease of calcium within one second) during the cardiac action potential. In this study, we demonstrated that cADPR levels higher than physiological levels induce a slow and gradual increase in the resting intracellular Ca²⁺ ([Ca²⁺](i)) level over 10 min by inhibiting the sarcoendoplasmic reticulum Ca²⁺ ATPase (SERCA). Higher cADPR levels mediate the tyrosine-dephosphorylation of α-actin by protein tyrosine phosphatase 1B (PTP1B) present in the endoplasmic reticulum. The tyrosine dephosphorylation of α-actin dissociates phospholamban, the key regulator of SERCA, from α-actin and results in SERCA inhibition. The disruption of the integrity of α-actin by cytochalasin B and the inhibition of α-actin tyrosine dephosphorylation by a PTP1B inhibitor block cADPR-mediated Ca²⁺ increase. Our results suggest that levels of cADPR that are relatively higher than normal physiological levels modify calcium homeostasis through the dephosphorylation of α-actin by PTB1B and the subsequent inhibition of SERCA in cardiac myocytes.
