Author/Editor		Mariggio, Stefania; Bavec, Aljoša; Natale, Elena; Zizza, Pasquale; Salmona, Mario; Corda, Daniela; Di Girolamo, Maria
Title		Galpha(13) mediates activation of the cytosolic phospholipase A(2)alpha through fine regulation of ERK phosphorylation
Type		članek
Source		Cell Signal
Vol. and No.		Letnik 18, št. 12
Publication year		2006
Volume		str. 2200-8
Language		eng
Abstract		Heterotrimeric GTP-binding (G) proteins transduce hormone-induced signals to their effector enzymes, which include several phospholipases. In particular, the G(o)/G(i) and G(q) protein families have been shown to couple signaling to phospholipase A(2) (PLA(2)), phospholipase C, and phospholipase D, while the G(12)/G(13) 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 G(12)/G(13) family is also able to activate cPLA(2)alpha, through the activation of RhoA and, subsequently, ERK1/2. Hormone-induced arachidonic acid release increased as a consequence of Galpha(13) overexpression, and was inhibited through inhibition of Galpha(13) signaling. The Galpha(13)-mediated cPLA(2)alpha 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 cPLA(2)alpha regulation that is initiated by thrombin and purinergic receptor activation, and that signals through Galpha(13), RhoA and ERK1/2, with the involvement of a calyculin-sensitive phosphatase.
Descriptors		CYTOSOL CHO CELLS PHOSPHOLIPASES A TRANSFECTION ARACHIDONIC ACID GTP-BINDING PROTEINS G-PROTEINS PHOSPHORYLATION THROMBIN ADENOSINE TRIPHOSPHATE RHO FACTOR