MAP KINASE PHOSPHATASE-3 AND ITS ALTERNATIVE SPLICE VARIANT ARE REGULATED BY ANGIOTENSIN II IN ADRENOCORTICAL CELL LINE H295R

MORI SEQUEIROS GARCIA M. MERCEDES; CALDERON LEON, KARIBAY; MELE, PABLO G.; COHEN SABBAN, JUAN M.; NUDLER, SILVANA I.; MALOBERTI, PAULA M.; PAZ, CRISTINA

Mar del Plata

Congreso; LXII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2018

Sociedad Argentina de Investigación Clínica

The concerted action of kinases and phosphatases regulates key biological events. MAP kinase phosphatases (MKP) regulate MAPK-dependent processes such as proliferation, differentiation and apoptosis. MKP-3 is induced by different proliferative stimuli and dephosphorylates ERK1/2. We studied MKP-3 expression and regulation by angiotensin II (AII) in a human adrenocortical cell line H295R. We evaluated AII effect on P-FOXO1 dephosphorylation (a novel MKP-3 substrate) and the induction of p21, a target for this transcription factor. The expression of both MKP-3 isoforms, MKP-3L and S, were up-regulated by AII. MKP-3L messenger levels reached a significant 2-fold increase after 30 min stimulation. MKP-3S mRNA levels were also significantly increased with a temporal profile similar to MKP-3L. Accordingly with MKP-3 effect, AII also regulates P-ERK1/2 levels. Moreover, P-FOXO1 levels increased rapidly after stimulation and decreased concomitantly with MKP-3 protein induction. Furthermore, we showed that AII upregulates p21, which is in agreement with the dephosphorylation and activation of P-FOXO1. In summary, our data suggest that AII regulates P-ERK levels, MKP-3 andMKP-3-related events. This regulation of MKP-3 involves mRNA increase in two MKP-3 transcripts. Thus, L and S variants of MKP-3 proteins could differentially regulate ERK-dependent events in adrenocortical cells upon AII stimulation