PTP ACTION AND ARACHIDONIC ACID RELEASE AS COMMON STEPS IN DIFFERENT SIGNAL PATHWAYS

P. MELE; F. CASTILLO; H. DI CONSOLI; I. NEUMAN; C. PAZ; F. CORNEJO MACIEL; E.J. PODESTÁ

Mar del Plata

Congreso; XLIII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2007

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

We have previously demonstrated the existence of a tyrosine phosphorylated protein necessary for the expression of an essential gene that promotes intramitochondrial cholesterol transport. This protein must be dephosphorylated by a protein tyrosine phosphatase (PTP) regulated through the cAMP/PKA pathway. Once dephosphorylated, the protein induces the expression of ACS4, an arachidonic acid (AA) preferring acyl-CoA synthetase, which acts in concert with Acot2, a long chain fatty acyl-CoA thioesterase, to promote AA release from mitochondria. Since compartmentalized AA release is activated by different pathways, we aimed to study if the PTP is a common step activated by these different pathways. We used H295R cells, a human adrenal cell line that responds to three different signal transduction pathways to release aldosterone. Using two different PTP inhibitors we have shown that PTP action was necessary for the stimulation of aldosterone synthesis by ACTH as well as by angiotensin II and K+. Inhibition of PTP activity was overcome by the addition of exogenous AA, supporting the notion that this activity is involved in AA release and aldosterone synthesis. These results suggest, by first time, that the PTP action and compartmentalized AA release are common steps in the mechanism of activation of steroid synthesis by different signal transduction pathways.