13 mediates activation of the cytosolic phospholipase A2α through fine regulation of ERK phosphorylation

Stefania Mariggiò, Aljosa Bavec, Elena Natale, Pasquale Zizza, Mario Salmona, Daniela Corda, Maria Di Girolamo

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Heterotrimeric GTP-binding (G) proteins transduce hormone-induced signals to their effector enzymes, which include several phospholipases. In particular, the Go/Gi and Gq protein families have been shown to couple signaling to phospholipase A2 (PLA2), phospholipase C, and phospholipase D, while the G12/G13 family has been linked to the activation of small GTPases of the Rho family, and hence, to phospholipase D activation. Here, we demonstrate that in CHO cells, the G12/G13 family is also able to activate cPLA2α, through the activation of RhoA and, subsequently, ERK1/2. Hormone-induced arachidonic acid release increased as a consequence of Gα13 overexpression, and was inhibited through inhibition of Gα13 signaling. The Gα13-mediated cPLA2α activation was inhibited by pharmacological blockade of ERK1/2 with either U0126 or PD98059, and by RhoA inactivation with C3 toxin or a dominant-negative RhoA (N19RhoA), and was stimulated by the serine-threonine phosphatase inhibitor calyculin A. Our data thus identify a pathway of cPLA2α regulation that is initiated by thrombin and purinergic receptor activation, and that signals through Gα13, RhoA and ERK1/2, with the involvement of a calyculin-sensitive phosphatase.

Original languageEnglish
Pages (from-to)2200-2208
Number of pages9
JournalCellular Signalling
Volume18
Issue number12
DOIs
Publication statusPublished - Dec 2006

Fingerprint

Cytosolic Phospholipases A2
Phospholipase D
Gq-G11 GTP-Binding Protein alpha Subunits
Phosphorylation
Hormones
Thrombin Receptors
Purinergic Receptors
Heterotrimeric GTP-Binding Proteins
Monomeric GTP-Binding Proteins
CHO Cells
Phospholipases
Phosphoprotein Phosphatases
Phospholipases A2
Type C Phospholipases
GTP-Binding Proteins
Phosphoric Monoester Hydrolases
Arachidonic Acid
Pharmacology
Enzymes
U 0126

Keywords

  • Arachidonic acid
  • ATP
  • CHO cells
  • cPLA
  • G proteins
  • G-protein-coupled receptors
  • Mitogen-activated protein kinase
  • Thrombin

ASJC Scopus subject areas

  • Cell Biology

Cite this

13 mediates activation of the cytosolic phospholipase A2α through fine regulation of ERK phosphorylation. / Mariggiò, Stefania; Bavec, Aljosa; Natale, Elena; Zizza, Pasquale; Salmona, Mario; Corda, Daniela; Di Girolamo, Maria.

In: Cellular Signalling, Vol. 18, No. 12, 12.2006, p. 2200-2208.

Research output: Contribution to journalArticle

Mariggiò, Stefania ; Bavec, Aljosa ; Natale, Elena ; Zizza, Pasquale ; Salmona, Mario ; Corda, Daniela ; Di Girolamo, Maria. / 13 mediates activation of the cytosolic phospholipase A2α through fine regulation of ERK phosphorylation. In: Cellular Signalling. 2006 ; Vol. 18, No. 12. pp. 2200-2208.
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