Phosphorylation and function of the hamster adrenal steroidogenic acute regulatory protein (StAR)

The Journal of Steroid Biochemistry and Molecular Biology
Alain FleuryJean-Guy LeHoux

Abstract

In order to study the effect of phosphorylation on the function of the steroidogenic acute regulatory protein (StAR), 10 putative phosphorylation sites were mutated in the hamster StAR. In pcDNA3.1-StAR transfected COS-1 cells, decreases in basal activity were found for the mutants S55A, S185A and S194A. Substitution of S185 by D or E to mimic phosphorylation resulted in decreased activity for all mutants; we concluded that S185 was not a phosphorylation site and we hypothesized that mutations on S185 created StAR conformational changes resulting in a decrease in its binding affinity for cholesterol. In contrast, the mutation S194D resulted in an increase in StAR activity. We have calculated the relative rate of pregnenolone formation (App. V(max)) in transfected COS-1 cells with wild type (WT) and mutant StAR-pcDNA3.1 under control and (Bu)(2)-cAMP stimulation. The App. V(max) values refer to the rate of cholesterol transported and metabolized by the cytochrome P450scc enzyme present in the inner mitochondrial membrane. The App. V(max) was 1.61 +/- 0.28 for control (Ctr) WT StAR and this value was significantly increased to 4.72 +/- 0.09 for (Bu)(2)-cAMP stimulated preparations. App. V(max) of 5.53 (Ctr) and 4.82 ((Bu)(2)-cAMP...Continue Reading

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Citations

Apr 25, 2007·International Journal of Obesity : Journal of the International Association for the Study of Obesity·A W KrugM Ehrhart-Bornstein
Nov 17, 2010·Reproductive Sciences·Vladimir E VargasCharles A Ducsay
Oct 4, 2011·The Journal of Endocrinology·Barbara J Clark
Jun 4, 2011·Journal of Signal Transduction·Pulak R Manna, Douglas M Stocco
Mar 10, 2015·Biology·Barbara J Clark, Elizabeth A Hudson
Aug 15, 2015·Endocrine·Pulak R MannaKevin Pruitt
Aug 16, 2011·Molecular and Cellular Endocrinology·Namita G HattangadyWilliam E Rainey
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Aug 3, 2013·Molecular and Cellular Endocrinology·László FülöpAndrás Spät
Sep 17, 2014·Molecular and Cellular Biology·Houssein S AbdouJacques J Tremblay
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Jun 20, 2019·Biochemistry. Biokhimii︠a︡·K V Tugaeva, N N Sluchanko

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