Role of protein phosphorylation and tyrosine phosphatases in the adrenal regulation of steroid synthesis and mitochondrial function

PAZ C; CORNEJO MACIEL F; GOROSTIZAGA AB; CASTILLO AF; MORI SEQUEIROS GARCÍA MM; MALOBERTI PM; ORLANDO U; MELE PG; PODEROSO C; PODESTA EJ

Frontiers in endocrinology

Frontiers Research Fundation

Año: 2016

In adrenocortical cells, adrenocorticotropin (ACTH) promotes the activation of several protein kinases. The action of these kinasesis linked to steroid production, mainly through steroidogenic acute regulatory protein (StAR), whose expression and activity aredependent on protein phosphorylation events at genomic and non-genomic levels. Hormone-dependent mitochondrial dynamics andcell proliferation are functions also associated with protein kinases. On the other hand, protein tyrosine dephosphorylation is anadditional component of the ACTH signaling pathway which involves the ?classical? protein tyrosine phosphatases (PTPs), such asSHP2 (src homology domain (SH) 2 containing PTP), and members of the MAP kinase phosphatase (MKP) family, such as MKP-1. PTPsare rapidly activated by post-translational mechanisms and participate in hormone-stimulated steroid production. In this process,the SHP2 tyrosine phosphatase plays a crucial role in a mechanism that includes an acyl-CoA synthetase-4 (Acsl4), arachidonic acid(AA) release and StAR induction. In contrast, MKPs in steroidogenic cells have a role in the turn-off of the hormonal signal inERK-dependent processes such as steroid synthesis and, perhaps, cell proliferation. This review analyzes the participation of thesetyrosine phosphates in the ACTH signaling pathway and the action of kinases and phosphatases in the regulation of mitochondrialdynamics and steroid production. In addition, the participation of kinases and phosphatases in the signal cascade triggered bydifferent stimuli in other steroidogenic tissues is also compared to adrenocortical cell/ACTH and discussed.