Role of Protein Phosphorylation and Tyrosine Phosphatases in the Adrenal Regulation of Steroid Synthesis and Mitochondrial Function

CRISTINA PAZ; FABIANA CORNEJO MACIEL; ANA F. CASTILLO; ALEJANDRA GOROSTIZAGA; M. MERCEDES MORI SEQUEIROS GARCÍA; PAULA M. MALOBERTI; ULISES D. ORLANDO; PABLO G. MELE; CECILIA PODEROSO; ERNESTO J. PODESTA

Frontiers in Endocrinology

Frontiers

Año: 2016 p. 1 - 10

In adrenocortical cells, adrenocorticotropin (ACTH) promotes the activation of severalprotein kinases. The action of these kinases is linked to steroid production, mainlythrough steroidogenic acute regulatory protein (StAR), whose expression and activityare dependent on protein phosphorylation events at genomic and non-genomic levels.Hormone-dependent mitochondrial dynamics and cell proliferation are functions alsoassociated with protein kinases. On the other hand, protein tyrosine dephosphorylationis an additional component of the ACTH signaling pathway, which involves the ?classical?protein tyrosine phosphatases (PTPs), such as Src homology domain (SH) 2-containingPTP (SHP2c), and members of the MAP kinase phosphatase (MKP) family, such asMKP-1. PTPs are rapidly activated by posttranslational mechanisms and participate inhormone-stimulated steroid production. In this process, the SHP2 tyrosine phosphataseplays a crucial role in a mechanism that includes an acyl-CoA synthetase-4 (Acsl4), arachidonicacid (AA) release and StAR induction. In contrast, MKPs in steroidogenic cellshave a role in the turn-off of the hormonal signal in ERK-dependent processes such assteroid synthesis and, perhaps, cell proliferation. This review analyzes the participationof these tyrosine phosphates in the ACTH signaling pathway and the action of kinasesand phosphatases in the regulation of mitochondrial dynamics and steroid production. Inaddition, the participation of kinases and phosphatases in the signal cascade triggeredby different stimuli in other steroidogenic tissues is also compared to adrenocortical cell/ACTH and discussed.