The tyrosine phosphatase SHP2 is a mediator of cAMP-stimulated StAR induction

COOKE, M.; MALOBERTI, P.; PODESTA, E.J.; CORNEJO MACIEL, F.

League City, Texas

Conferencia; XXth Adrenal Cortex Conference; 2012

Adrenal Cortex Conference

SHP2 is an ubiquitously expressed non-transmembrane protein tyrosine phosphatase (PTP). It is one of the PTPs that promote the activation, rather than the down-regulation of intracellular signaling pathways, serving multiple hormone receptors. It is activated by phosphorylation and it is related to the induction of the acyl-CoA synthetase Acsl4. We tested whether SHP2 is the PTP involved in the regulation of StAR induction. Modifications in SHP2 protein levels affected the steroidogenic capacity of MA-10 cells: overexpression or knock-down of SHP2 caused an increase or decrease in StAR protein levels and progesterone production. SHP2 has to be present and activated by a cAMP-dependent pathway since the overexpression of a catalytically inactive form of the enzyme (CS-SHP2) did not reproduce the stimulatory effects of the wild-type form on Acsl4 and StAR protein levels and on steroidogenesis. The effect could be specifically attributed to SHP2 since knock-down of this PTP by specific shRNA reduced Acsl4 and StAR mRNAs and protein levels as well as progesterone production. In conclusion, SHP2 is a key enzyme that affects the expression of Acsl4 and StAR, two rate limiting proteins in the acute stimulation of steroidogenesis.