RGD Reference Report - Novel function of cardiac protein kinase D1 as a dynamic regulator of Ca2+ sensitivity of contraction. - Rat Genome Database

RGD Reference Report - Novel function of cardiac protein kinase D1 as a dynamic regulator of Ca2+ sensitivity of contraction. - Rat Genome Database

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Novel function of cardiac protein kinase D1 as a dynamic regulator of Ca2+ sensitivity of contraction.
Authors:	Goodall, Mariah H Wardlow, Robert D Goldblum, Rebecca R Ziman, Andrew Lederer, W Jonathan Randall, William Rogers, Terry B
Citation:	Goodall MH, etal., J Biol Chem. 2010 Dec 31;285(53):41686-700. doi: 10.1074/jbc.M110.179648. Epub 2010 Nov 1.
RGD ID:	243065274
Pubmed:	PMID:21041300 (View Abstract at PubMed)
PMCID:	PMC3009896 (View Article at PubMed Central)
DOI:	DOI:10.1074/jbc.M110.179648 (Journal Full-text)
Although the function of protein kinase D1 (PKD) in cardiac cells has remained enigmatic, recent work has shown that PKD phosphorylates the nuclear regulators HDAC5/7 (histone deacetylase 5/7) and CREB, implicating this kinase in the development of dysfunction seen in heart failure. Additional studies have shown that PKD also phosphorylates multiple sarcomeric substrates to regulate myofilament function. Initial studies examined PKD through adenoviral vector expression of wild type PKD, constitutively active PKD (caPKD), or dominant negative PKD in cultured adult rat ventricular myocytes. Confocal immunofluorescent images of these cells reveal a predominant distribution of all PKD forms in a non-nuclear, Z-line localized, striated reticular pattern, suggesting the importance of PKD in Ca(2+) signaling in heart. Consistent with an established role of PKD in targeting cardiac troponin I (cTnI), caPKD expression led to a marked decrease in contractile myofilament Ca(2+) sensitivity with an unexpected electrical stimulus dependence to this response. This desensitization was accompanied by stimulus-dependent increases in cTnI phosphorylation in control and caPKD cells with a more pronounced effect in the latter. Electrical stimulation also provoked phosphorylation of regulatory site Ser(916) on PKD. The functional importance of this phospho-Ser(916) event is demonstrated in experiments with a phosphorylation-defective mutant, caPKD-S916A, which is functionally inactive and blocks stimulus-dependent increases in cTnI phosphorylation. Dominant negative PKD expression resulted in sensitization of the myofilaments to Ca(2+) and blocked stimulus-dependent increases in cTnI phosphorylation. Taken together, these data reveal that localized PKD may play a role as a dynamic regulator of Ca(2+) sensitivity of contraction in cardiac myocytes.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Prkd1	Rat	positive regulation of peptidyl-serine phosphorylation		IMP			RGD
Prkd1	Rat	regulation of skeletal muscle contraction by modulation of calcium ion sensitivity of myofibril		IMP			RGD

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Genes (Rattus norvegicus)

Prkd1 (protein kinase D1)

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