Protein kinase C and Src family kinases mediate angiotensin II-induced protein kinase D activation and acute aldosterone production

Lawrence O. Olala, Brian A. Shapiro, Todd David Merchen, James J. Wynn, Wendy B Bollag

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Recent evidence has shown a role for the serine/threonine protein kinase D (PKD) in the regulation of acute aldosterone secretion upon angiotensin II (AngII) stimulation. However, the mechanism by which AngII activates PKD remains unclear. In this study, using both pharmacological and molecular approaches, we demonstrate that AngII-induced PKD activation is mediated by protein kinase C (PKC) and Src family kinases in primary bovine adrenal glomerulosa cells and leads to increased aldosterone production. The pan PKC inhibitor Ro 31-8220 and the Src family kinase inhibitors PP2 and Src-1 inhibited both PKD activation and acute aldosterone production. Additionally, like the dominant-negative serine-738/742-to-alanine PKD mutant that cannot be phosphorylated by PKC, the dominant-negative tyrosine-463-to-phenylalanine PKD mutant, which is not phosphorylatable by the Src/Abl pathway, inhibited acute AngII-induced aldosterone production. Taken together, our results demonstrate that AngII activates PKD via a mechanism involving Src family kinases and PKC, to underlie increased aldosterone production.

Original languageEnglish (US)
Pages (from-to)173-181
Number of pages9
JournalMolecular and Cellular Endocrinology
Volume392
Issue number1-2
DOIs
StatePublished - Jul 5 2014

Fingerprint

src-Family Kinases
Aldosterone
Angiotensin II
Protein Kinase C
Chemical activation
Zona Glomerulosa
Protein C Inhibitor
Protein-Serine-Threonine Kinases
Protein Kinase Inhibitors
protein kinase D
Phenylalanine
Alanine
Serine
Tyrosine
Pharmacology

Keywords

  • Adrenal glomerulosa
  • Aldosterone
  • Angiotensin II (AngII)
  • Protein kinase C (PKC)
  • Protein kinase D (PKD)
  • Src family kinases

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

Protein kinase C and Src family kinases mediate angiotensin II-induced protein kinase D activation and acute aldosterone production. / Olala, Lawrence O.; Shapiro, Brian A.; Merchen, Todd David; Wynn, James J.; Bollag, Wendy B.

In: Molecular and Cellular Endocrinology, Vol. 392, No. 1-2, 05.07.2014, p. 173-181.

Research output: Contribution to journalArticle

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