Angiotensin II-Induced protein kinase D activates the ATF/CREB family of transcription factors and promotes StAR mRNA expression

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Aldosterone synthesis is initiated upon the transport of cholesterol from the outer to the inner mitochondrial membrane, where the cholesterol is hydrolyzed to pregnenolone. This process is the rate-limiting step in acute aldosterone production and is mediated by the steroidogenic acute regulatory (StAR) protein. We have previously shown that angiotensin II (AngII) activation of the serine/threonine protein kinase D (PKD) promotes acute aldosterone production in bovine adrenal glomerulosa cells, but the mechanism remains unclear. Thus, the purpose of this study was to determine the downstream signaling effectors of AngII-stimulated PKD activity. Our results demonstrate that overexpression of the constitutively active serine-to-glutamate PKD mutant enhances, whereas the dominant-negative serine-to-alanine PKD mutant inhibits, AngII-induced StAR mRNA expression relative to the vector control. PKD has been shown to phosphorylate members of the activating transcription factor (ATF)/cAMP response element binding protein (CREB) family of leucine zipper transcription factors, which have been shown previously to bind the StAR proximal promoter and induce StAR mRNA expression. In primary glomerulosa cells, AngII induces ATF-2 and CREB phosphorylation in a time-dependent manner. Furthermore, overexpression of the constitutively active PKD mutant enhances the AngII-elicited phosphorylation of ATF-2 and CREB, and the dominant-negative mutant inhibits this response. Furthermore, the constitutively active PKD mutant increases the binding of phosphorylated CREB to the StAR promoter. Thus, these data provide insight into the previously reported role of PKD in AngII-induced acute aldosterone production, providing a mechanism by which PKD maybe mediating steroidogenesis in primary bovine adrenal glomerulosa cells.

Original languageEnglish (US)
Pages (from-to)2524-2533
Number of pages10
JournalEndocrinology
Volume155
Issue number7
DOIs
StatePublished - Jan 1 2014

Fingerprint

Activating Transcription Factors
Cyclic AMP Response Element-Binding Protein
Angiotensin II
Transcription Factors
Messenger RNA
Aldosterone
Activating Transcription Factor 2
Zona Glomerulosa
glutamate 5-kinase
Serine
Cholesterol
Phosphorylation
protein kinase D
Leucine Zippers
Pregnenolone
Protein-Serine-Threonine Kinases
Mitochondrial Membranes
Alanine

ASJC Scopus subject areas

  • Endocrinology

Cite this

@article{9049095af965437b848aacde31db9130,
title = "Angiotensin II-Induced protein kinase D activates the ATF/CREB family of transcription factors and promotes StAR mRNA expression",
abstract = "Aldosterone synthesis is initiated upon the transport of cholesterol from the outer to the inner mitochondrial membrane, where the cholesterol is hydrolyzed to pregnenolone. This process is the rate-limiting step in acute aldosterone production and is mediated by the steroidogenic acute regulatory (StAR) protein. We have previously shown that angiotensin II (AngII) activation of the serine/threonine protein kinase D (PKD) promotes acute aldosterone production in bovine adrenal glomerulosa cells, but the mechanism remains unclear. Thus, the purpose of this study was to determine the downstream signaling effectors of AngII-stimulated PKD activity. Our results demonstrate that overexpression of the constitutively active serine-to-glutamate PKD mutant enhances, whereas the dominant-negative serine-to-alanine PKD mutant inhibits, AngII-induced StAR mRNA expression relative to the vector control. PKD has been shown to phosphorylate members of the activating transcription factor (ATF)/cAMP response element binding protein (CREB) family of leucine zipper transcription factors, which have been shown previously to bind the StAR proximal promoter and induce StAR mRNA expression. In primary glomerulosa cells, AngII induces ATF-2 and CREB phosphorylation in a time-dependent manner. Furthermore, overexpression of the constitutively active PKD mutant enhances the AngII-elicited phosphorylation of ATF-2 and CREB, and the dominant-negative mutant inhibits this response. Furthermore, the constitutively active PKD mutant increases the binding of phosphorylated CREB to the StAR promoter. Thus, these data provide insight into the previously reported role of PKD in AngII-induced acute aldosterone production, providing a mechanism by which PKD maybe mediating steroidogenesis in primary bovine adrenal glomerulosa cells.",
author = "Olala, {Lawrence O.} and Vivek Choudhary and Johnson, {Maribeth H} and Bollag, {Wendy B}",
year = "2014",
month = "1",
day = "1",
doi = "10.1210/en.2013-1485",
language = "English (US)",
volume = "155",
pages = "2524--2533",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "7",

}

TY - JOUR

T1 - Angiotensin II-Induced protein kinase D activates the ATF/CREB family of transcription factors and promotes StAR mRNA expression

AU - Olala, Lawrence O.

AU - Choudhary, Vivek

AU - Johnson, Maribeth H

AU - Bollag, Wendy B

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Aldosterone synthesis is initiated upon the transport of cholesterol from the outer to the inner mitochondrial membrane, where the cholesterol is hydrolyzed to pregnenolone. This process is the rate-limiting step in acute aldosterone production and is mediated by the steroidogenic acute regulatory (StAR) protein. We have previously shown that angiotensin II (AngII) activation of the serine/threonine protein kinase D (PKD) promotes acute aldosterone production in bovine adrenal glomerulosa cells, but the mechanism remains unclear. Thus, the purpose of this study was to determine the downstream signaling effectors of AngII-stimulated PKD activity. Our results demonstrate that overexpression of the constitutively active serine-to-glutamate PKD mutant enhances, whereas the dominant-negative serine-to-alanine PKD mutant inhibits, AngII-induced StAR mRNA expression relative to the vector control. PKD has been shown to phosphorylate members of the activating transcription factor (ATF)/cAMP response element binding protein (CREB) family of leucine zipper transcription factors, which have been shown previously to bind the StAR proximal promoter and induce StAR mRNA expression. In primary glomerulosa cells, AngII induces ATF-2 and CREB phosphorylation in a time-dependent manner. Furthermore, overexpression of the constitutively active PKD mutant enhances the AngII-elicited phosphorylation of ATF-2 and CREB, and the dominant-negative mutant inhibits this response. Furthermore, the constitutively active PKD mutant increases the binding of phosphorylated CREB to the StAR promoter. Thus, these data provide insight into the previously reported role of PKD in AngII-induced acute aldosterone production, providing a mechanism by which PKD maybe mediating steroidogenesis in primary bovine adrenal glomerulosa cells.

AB - Aldosterone synthesis is initiated upon the transport of cholesterol from the outer to the inner mitochondrial membrane, where the cholesterol is hydrolyzed to pregnenolone. This process is the rate-limiting step in acute aldosterone production and is mediated by the steroidogenic acute regulatory (StAR) protein. We have previously shown that angiotensin II (AngII) activation of the serine/threonine protein kinase D (PKD) promotes acute aldosterone production in bovine adrenal glomerulosa cells, but the mechanism remains unclear. Thus, the purpose of this study was to determine the downstream signaling effectors of AngII-stimulated PKD activity. Our results demonstrate that overexpression of the constitutively active serine-to-glutamate PKD mutant enhances, whereas the dominant-negative serine-to-alanine PKD mutant inhibits, AngII-induced StAR mRNA expression relative to the vector control. PKD has been shown to phosphorylate members of the activating transcription factor (ATF)/cAMP response element binding protein (CREB) family of leucine zipper transcription factors, which have been shown previously to bind the StAR proximal promoter and induce StAR mRNA expression. In primary glomerulosa cells, AngII induces ATF-2 and CREB phosphorylation in a time-dependent manner. Furthermore, overexpression of the constitutively active PKD mutant enhances the AngII-elicited phosphorylation of ATF-2 and CREB, and the dominant-negative mutant inhibits this response. Furthermore, the constitutively active PKD mutant increases the binding of phosphorylated CREB to the StAR promoter. Thus, these data provide insight into the previously reported role of PKD in AngII-induced acute aldosterone production, providing a mechanism by which PKD maybe mediating steroidogenesis in primary bovine adrenal glomerulosa cells.

UR - http://www.scopus.com/inward/record.url?scp=84902245711&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902245711&partnerID=8YFLogxK

U2 - 10.1210/en.2013-1485

DO - 10.1210/en.2013-1485

M3 - Article

C2 - 24708239

AN - SCOPUS:84902245711

VL - 155

SP - 2524

EP - 2533

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 7

ER -