Human heart failure is accompanied by altered protein kinase A subunit expression and post-translational state

Young Soo Han, Jennifer Arroyo, Ozgur Ogut

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

β-Adrenergic receptor blockade reduces total mortality and all-cause hospitalizations in patients with heart failure (HF). Nonetheless, β-blockade does not halt disease progression, suggesting that cAMP-dependent protein kinase (PKA) signaling downstream of β-adrenergic receptor activation may persist through unique post-translational states. In this study, human myocardial tissue was used to examine the state of PKA subunits. As expected, total myosin binding protein-C phosphorylation and Ser23/24 troponin I phosphorylation significantly decreased in HF. Examination of PKA subunits demonstrated no change in type II regulatory (RIIα) or catalytic (Cα) subunit expression, although site specific RIIα (Ser96) and Cα (Thr197) phosphorylation were increased in HF. Further, the expression of type I regulatory subunit (RI) was increased in HF. Isoelectric focusing of RIα demonstrated up to three variants, consistent with reports that Ser77 and Ser83 are in vivo phosphorylation sites. Western blots with site-specific monoclonal antibodies showed increased Ser83 phosphorylation in HF. 8-fluo-cAMP binding by wild type and phosphomimic Ser77 and Ser83 mutant RIα proteins demonstrated reduced Kd for the double mutant as compared to WT RIα. Therefore, failing myocardium displays altered expression and post-translational modification of PKA subunits that may impact downstream signaling.

Original languageEnglish (US)
Pages (from-to)25-33
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume538
Issue number1
DOIs
StatePublished - 2013

Fingerprint

Phosphorylation
Cyclic AMP-Dependent Protein Kinases
Heart Failure
Protein Subunits
Protein Kinases
Adrenergic Receptors
Troponin I
Isoelectric Focusing
Mutant Proteins
Post Translational Protein Processing
Disease Progression
Catalytic Domain
Myocardium
Hospitalization
Western Blotting
Chemical activation
Display devices
Monoclonal Antibodies
Tissue
Mortality

Keywords

  • Catalytic
  • Heart
  • Phosphorylation
  • Protein kinase A
  • Regulatory

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Human heart failure is accompanied by altered protein kinase A subunit expression and post-translational state. / Han, Young Soo; Arroyo, Jennifer; Ogut, Ozgur.

In: Archives of Biochemistry and Biophysics, Vol. 538, No. 1, 2013, p. 25-33.

Research output: Contribution to journalArticle

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