Phosphotyrosine protein phosphatases activation by ACTH in rat adrenal gland

The steady state level of most cellular phosphoproteins is dependent on the relative catalytic activities of intracellular protein kinases and phospha tases. In adrenal cortex, ACTH acts through PKA activation and Ser/Tre phos phorylation. Phosphatases involved in this pathway are not completely descr ibed particularly the role of phosphotyrosine protein phosphatase (PTP) act ivity on ACTH action.. We investigated potential changes in PTPs activity i n adrenal gland upon in vivo and in vitro PKA activation. In vivo ACTH stim ulates cytosolic PTP activity (2-fold). Similar effect is detected by in vi tro stimulation. In accordance with the effects of ACTH on PTP activity, ce ll permeable PTP inhibitors block ACTH stimulation on adrenal zona fascicul ata (ZF) cells: ACTH (1 nM) = 108.2 +/- 3.5 ng corticosterone/10(5) cells v s. ACTH + phenylarsine oxide (2 nM) = 60 +/- 4 (P < 0,001) and ACTH + perva nadate (10 mM) = 68 +/- 2 (P < 0,01). These results are reproduced when cel ls are stimulated with cAMP. The inhibition is not observed when steroidoge nesis is supported by 22(R)OH cholesterol. We describe, for the first time, a hormonal regulation of PTP activity. According to the effect of PTP inhi bitors on steroid production activated by ACTH we propose that PTP activati on is a crucial event in hormone action in the steroidogenic pathway. We al so propose that PTP activity is located after PKA activation and prior to c holesterol transport to the inner mitochondrial membrane.