A novel protein kinase C target site in protein kinase D is phosphorylated in response to signals for cardiac hypertrophy
| Autor: | Q. Khai Huynh, Timothy A. McKinsey, Dillon Phan, Matthew S. Stratton |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Molecular Sequence Data
Biophysics Cardiomegaly Biology Biochemistry Serine Norepinephrine Humans Myocytes Cardiac Amino Acid Sequence Phosphorylation Receptor Molecular Biology Protein kinase C Protein Kinase C G protein-coupled receptor Endothelin-1 Kinase HEK 293 cells Cell Biology musculoskeletal system Molecular biology Pleckstrin homology domain HEK293 Cells cardiovascular system |
| Zdroj: | Biochemical and biophysical research communications. 411(2) |
| ISSN: | 1090-2104 |
| Popis: | Protein kinase D (PKD) regulates cardiac myocyte growth and contractility through phosphorylation of proteins such as class IIa histone deacetylases (HDACs) and troponin I (TnI). In response to agonists that activate G-protein-coupled receptors (GPCRs), PKD is phosphorylated by protein kinase C (PKC) on two serine residues (Ser-738 and Ser-742 in human PKD1) within an activation loop of the catalytic domain, resulting in stimulation of PKD activity. Here, we identify a novel PKC target site located adjacent to the auto-inhibitory pleckstrin homology (PH) domain in PKD. This site (Ser-412 in human PKD1) is conserved in each of the three PKD family members and is efficiently phosphorylated by multiple PKC isozymes in vitro. Employing a novel anti-phospho-Ser-412-specific antibody, we demonstrate that this site in PKD is rapidly phosphorylated in primary cardiac myocytes exposed to hypertrophic agonists, including norepinephrine (NE) and endothelin-1 (ET-1). Differential sensitivity of this event to pharmacological inhibitors of PKC, and data from in vitro enzymatic assays, suggest a predominant role for PKCδ in the control of PKD Ser-412 phosphorylation. Together, these data suggest a novel, signal-dependent mechanism for controlling PKD function in cardiac myocytes. |
| Databáze: | OpenAIRE |
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