IDENTIFICATION OF THE TYROSINE PHOSPHATASE RESPONSIBLE FOR HORMONAL INDUCTION OF ACSL4, StAR AND CHOLESTEROL TRANSPORT.

ERNESTO J PODESTA

San Diego

Simposio; XIIth Adrenal Cortex and Vth Molecular Steroidogenesis Conference; 2010

National Institutes of Health

LH/CG-, ACTH-, Angiotensin- or Potassium-dependent stimulation of steroidogenesis in Leydig cells, adrenal zona fasciculata or zona glomerulosa cells respectively is dependent on tyrosine phosphatase activity regulated by different signal transduction pathways. The activation of tyrosine phosphatases is also necessary for the induction of an acyl-CoA synthetase that is the rate-limiting enzyme in the generation of intramitochondrial arachidonic acid and StAR induction. In addition, the action of tyrosine phosphatases on StAR promoter activity is mediated by arachidonic acid. Using an in gel phosphatase assay we have partially characterized three ACTH-dependent tyrosine phosphatases with molecular masses of 50, 80 and 110-115 kDa. Recently we have identified the 80 and 120 kDa proteins as SHP2 and PTP-PEST respectively. SHP2 is one of the phosphatases that it is activated by protein phosphorylation and one of the rare tyrosine phosphatases that promotes activation rather than down-regulation of intracellular signaling pathways. However the mechanism of action of SHP2 is as yet not fully understood. In this study we present data showing the role of SHP2 in the regulation of the rate-limiting step in steroid synthesis: the transport of cholesterol from the outer to the inner mitochondria membrane.