Amplification of Ca2+ signaling by diacylglycerol-mediated inositol 1,4,5-trisphosphate production

Chihiro Hisatsune, Kyoko Nakamura, Yukiko Kuroda, Takeshi Nakamura, Katsuhiko Mikoshiba

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Stimulation of various cell surface receptors leads to the production of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) through phospholipase C (PLC) activation, and the IP3 and DAG in turn trigger Ca2+ release through IP3 receptors and protein kinase C activation, respectively. The amount of IP3 produced is particularly critical to determining the spatio-temporally coordinated Ca2+- signaling patterns. In this paper, we report a novel signal cross-talk between DAG and the IP3-mediated Ca2+-signaling pathway. We found that a DAG derivative, 1-oleoyl-2-acyl-sn-glycerol (OAG), induces Ca 2+ oscillation in various types of cells independently of protein kinase C activity and extracellular Ca2+. The OAG-induced Ca 2+ oscillation was completely abolished by depletion of Ca 2+ scores or inhibition of PLC and IP3 receptors, indicating that OAG stimulates IP3 production through PLC activation and thereby induces IP3-induced Ca2+ release. Furthermore, intracellular accumulation of endogenous DAG by a DAG-lipase inhibitor greatly increased the number of cells responding to agonist stimulation at low doses. These results suggest a novel physiological function of DAG, i.e. amplification of Ca2+ signaling by enhancing [P3 production via its positive feedback effect on PLC activity.

Original languageEnglish
Pages (from-to)11723-11730
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number12
DOIs
Publication statusPublished - 2005 Mar 25
Externally publishedYes

Fingerprint

Inositol 1,4,5-Trisphosphate
Diglycerides
Amplification
Type C Phospholipases
Glycerol
Inositol 1,4,5-Trisphosphate Receptors
Chemical activation
Protein Kinase C
Lipoprotein Lipase
Cell Surface Receptors
Cell Count
Derivatives
Feedback

ASJC Scopus subject areas

  • Biochemistry

Cite this

Amplification of Ca2+ signaling by diacylglycerol-mediated inositol 1,4,5-trisphosphate production. / Hisatsune, Chihiro; Nakamura, Kyoko; Kuroda, Yukiko; Nakamura, Takeshi; Mikoshiba, Katsuhiko.

In: Journal of Biological Chemistry, Vol. 280, No. 12, 25.03.2005, p. 11723-11730.

Research output: Contribution to journalArticle

Hisatsune, Chihiro ; Nakamura, Kyoko ; Kuroda, Yukiko ; Nakamura, Takeshi ; Mikoshiba, Katsuhiko. / Amplification of Ca2+ signaling by diacylglycerol-mediated inositol 1,4,5-trisphosphate production. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 12. pp. 11723-11730.
@article{dcac61f29d6044829fb1c376e50a0804,
title = "Amplification of Ca2+ signaling by diacylglycerol-mediated inositol 1,4,5-trisphosphate production",
abstract = "Stimulation of various cell surface receptors leads to the production of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) through phospholipase C (PLC) activation, and the IP3 and DAG in turn trigger Ca2+ release through IP3 receptors and protein kinase C activation, respectively. The amount of IP3 produced is particularly critical to determining the spatio-temporally coordinated Ca2+- signaling patterns. In this paper, we report a novel signal cross-talk between DAG and the IP3-mediated Ca2+-signaling pathway. We found that a DAG derivative, 1-oleoyl-2-acyl-sn-glycerol (OAG), induces Ca 2+ oscillation in various types of cells independently of protein kinase C activity and extracellular Ca2+. The OAG-induced Ca 2+ oscillation was completely abolished by depletion of Ca 2+ scores or inhibition of PLC and IP3 receptors, indicating that OAG stimulates IP3 production through PLC activation and thereby induces IP3-induced Ca2+ release. Furthermore, intracellular accumulation of endogenous DAG by a DAG-lipase inhibitor greatly increased the number of cells responding to agonist stimulation at low doses. These results suggest a novel physiological function of DAG, i.e. amplification of Ca2+ signaling by enhancing [P3 production via its positive feedback effect on PLC activity.",
author = "Chihiro Hisatsune and Kyoko Nakamura and Yukiko Kuroda and Takeshi Nakamura and Katsuhiko Mikoshiba",
year = "2005",
month = "3",
day = "25",
doi = "10.1074/jbc.M409535200",
language = "English",
volume = "280",
pages = "11723--11730",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "12",

}

TY - JOUR

T1 - Amplification of Ca2+ signaling by diacylglycerol-mediated inositol 1,4,5-trisphosphate production

AU - Hisatsune, Chihiro

AU - Nakamura, Kyoko

AU - Kuroda, Yukiko

AU - Nakamura, Takeshi

AU - Mikoshiba, Katsuhiko

PY - 2005/3/25

Y1 - 2005/3/25

N2 - Stimulation of various cell surface receptors leads to the production of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) through phospholipase C (PLC) activation, and the IP3 and DAG in turn trigger Ca2+ release through IP3 receptors and protein kinase C activation, respectively. The amount of IP3 produced is particularly critical to determining the spatio-temporally coordinated Ca2+- signaling patterns. In this paper, we report a novel signal cross-talk between DAG and the IP3-mediated Ca2+-signaling pathway. We found that a DAG derivative, 1-oleoyl-2-acyl-sn-glycerol (OAG), induces Ca 2+ oscillation in various types of cells independently of protein kinase C activity and extracellular Ca2+. The OAG-induced Ca 2+ oscillation was completely abolished by depletion of Ca 2+ scores or inhibition of PLC and IP3 receptors, indicating that OAG stimulates IP3 production through PLC activation and thereby induces IP3-induced Ca2+ release. Furthermore, intracellular accumulation of endogenous DAG by a DAG-lipase inhibitor greatly increased the number of cells responding to agonist stimulation at low doses. These results suggest a novel physiological function of DAG, i.e. amplification of Ca2+ signaling by enhancing [P3 production via its positive feedback effect on PLC activity.

AB - Stimulation of various cell surface receptors leads to the production of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) through phospholipase C (PLC) activation, and the IP3 and DAG in turn trigger Ca2+ release through IP3 receptors and protein kinase C activation, respectively. The amount of IP3 produced is particularly critical to determining the spatio-temporally coordinated Ca2+- signaling patterns. In this paper, we report a novel signal cross-talk between DAG and the IP3-mediated Ca2+-signaling pathway. We found that a DAG derivative, 1-oleoyl-2-acyl-sn-glycerol (OAG), induces Ca 2+ oscillation in various types of cells independently of protein kinase C activity and extracellular Ca2+. The OAG-induced Ca 2+ oscillation was completely abolished by depletion of Ca 2+ scores or inhibition of PLC and IP3 receptors, indicating that OAG stimulates IP3 production through PLC activation and thereby induces IP3-induced Ca2+ release. Furthermore, intracellular accumulation of endogenous DAG by a DAG-lipase inhibitor greatly increased the number of cells responding to agonist stimulation at low doses. These results suggest a novel physiological function of DAG, i.e. amplification of Ca2+ signaling by enhancing [P3 production via its positive feedback effect on PLC activity.

UR - http://www.scopus.com/inward/record.url?scp=15744396282&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=15744396282&partnerID=8YFLogxK

U2 - 10.1074/jbc.M409535200

DO - 10.1074/jbc.M409535200

M3 - Article

VL - 280

SP - 11723

EP - 11730

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 12

ER -