Phosphotyrosine protein phosphatases activation by ACTH in rat adrenal gland.

Abstract:

:The steady state level of most cellular phosphoproteins is dependent on the relative catalytic activities of intracellular protein kinases and phosphatases. In adrenal cortex, ACTH acts through PKA activation and Ser/Tre phosphorylation. Phosphatases involved in this pathway are not completely described, particularly the role of phosphotyrosine protein phosphatase (PTP) activity on ACTH action. We investigated potential changes in PTPs activity in adrenal gland upon in vivo and in vitro PKA activation. In vivo ACTH stimulates cytosolic PTP activity (2-fold). Similar effect is detected by in vitro stimulation. In accordance with the effects of ACTH on PTP activity, cell permeable PTP inhibitors block ACTH stimulation on adrenal zona fasciculata (ZF) cells: ACTH (1 nM) = 108.2 +/- 3.5 ng corticosterone/10(5) cells vs. ACTH + phenylarsine oxide (2 nM) = 60 +/- 4 (P < 0.001) and ACTH + pervanadate (10 mM) = 68 +/- 2 (P < 0.01). These results are reproduced when cells are stimulated with cAMP. The inhibition is not observed when steroidogenesis 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 inhibitors on steroid production activated by ACTH we propose that PTP activation is a crucial event in hormone action in the steroidogenic pathway. We also propose that PTP activity is located after PKA activation and prior to cholesterol transport to the inner mitochondrial membrane.

journal_name

Endocr Res

journal_title

Endocrine research

authors

Cornejo Maciel F,Paz C,Neuman MI,Podestá EJ

doi

10.3109/07435809809032618

subject

Has Abstract

pub_date

1998-08-01 00:00:00

pages

381-6

issue

3-4

eissn

0743-5800

issn

1532-4206

journal_volume

24

pub_type

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