Avtor/Urednik | Mariggio, Stefania; Bavec, Aljoša; Natale, Elena; Zizza, Pasquale; Salmona, Mario; Corda, Daniela; Di Girolamo, Maria | |
Naslov | Galpha(13) mediates activation of the cytosolic phospholipase A(2)alpha through fine regulation of ERK phosphorylation | |
Tip | članek | |
Vir | Cell Signal | |
Vol. in št. | Letnik 18, št. 12 | |
Leto izdaje | 2006 | |
Obseg | str. 2200-8 | |
Jezik | eng | |
Abstrakt | 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. | |
Deskriptorji | CYTOSOL CHO CELLS PHOSPHOLIPASES A TRANSFECTION ARACHIDONIC ACID GTP-BINDING PROTEINS G-PROTEINS PHOSPHORYLATION THROMBIN ADENOSINE TRIPHOSPHATE RHO FACTOR |