A role for calcium in sphingosine 1-phosphate-induced phospholipase D activity in C2C12 myoblasts.
Receptor-regulated phospholipase D (PLD) is a key signaling pathway implicated in the control of fundamental biological processes. Here evidence is presented that in addition to protein kinase C (PKC) and Rho GTPases, Ca(2+) response evoked by sphingosine 1-phosphate (S1P) also participates to the enzyme regulation. Ca(2+) was found critical for PKC(alpha)-mediated PLD activation. Moreover, S1P-induced PLD activity resulted diminished by calmodulin inhibitors such as W-7 and CGS9343B implicating its involvement in the process. A plausible candidate for Ca(2+)-dependent PLD regulation by S1P was represented by calcineurin, in view of the observed reduction of the stimulatory effect by cyclosporin A. In contrast, monomeric GTP-binding protein Ral was translocated to membranes by S1P in a Ca(2+)-independent manner, ruling out its possible role in agonist-mediated regulation of PLD.
Meacci
Elisabetta
E
Dipartimento di Scienze Biochimiche, Università di Firenze, Viale G.B. Morgagni 50, 50134 Firenze, Italy.
Becciolini
Laura
L
Nuti
Francesca
F
Donati
Chiara
C
Cencetti
Francesca
F
Farnararo
Marta
M
Bruni
Paola
P
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D008246:Lysophospholipids; D051379:Mice; D010739:Phospholipase D / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D051571:Protein Kinase C-alpha; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism*
D002614:Chelating Agents; D007476:Ionophores; D007527:Isoenzymes; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D000001:Calcimycin; D004533:Egtazic Acid; C496630:Prkca protein, mouse; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D010739:Phospholipase D; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D013110:Sphingosine; D002118:Calcium