title: Agonist activated PKCβII translocation and modulation of cardiac myocyte contractile function.
abstract: Elevated protein kinase C βII (PKCβII) expression develops during heart failure and yet the role of this isoform in modulating contractile function remains controversial. The present study examines the impact of agonist-induced PKCβII activation on contractile function in adult cardiac myocytes. Diminished contractile function develops in response to low dose phenylephrine (PHE, 100 nM) in controls, while function is preserved in response to PHE in PKCβII-expressing myocytes. PHE also caused PKCβII translocation and a punctate distribution pattern in myocytes expressing this isoform. The preserved contractile function and translocation responses to PHE are blocked by the inhibitor, LY379196 (30 nM) in PKCβII-expressing myocytes. Further analysis showed downstream protein kinase D (PKD) phosphorylation and phosphatase activation are associated with the LY379196-sensitive contractile response. PHE also triggered a complex pattern of end-target phosphorylation in PKCβII-expressing myocytes. These patterns are consistent with bifurcated activation of downstream signaling activity by PKCβII.
authors.affiliation: Department of Cardiac Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Hyosook
authors.initials: H
authors.lastname: Hwang
authors.forename: Dustin
authors.initials: D
authors.lastname: Robinson
authors.forename: Julie B
authors.initials: JB
authors.lastname: Rogers
authors.forename: Tamara K
authors.initials: TK
authors.lastname: Stevenson
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Lang
authors.forename: Sakthivel
authors.initials: S
authors.lastname: Sadayappan
authors.forename: Sharlene M
authors.initials: SM
authors.lastname: Day
authors.forename: Sivaraj
authors.initials: S
authors.lastname: Sivaramakrishnan
authors.forename: Margaret V
authors.initials: MV
authors.lastname: Westfall
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D008297:Male; D032342:Muscle Cells / Q000201:enzymology*; D009200:Myocardial Contraction; D010766:Phosphorylation; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D064546:Protein Kinase C beta; D021381:Protein Transport; D051381:Rats
chemical_list: D011493:Protein Kinase C; D064546:Protein Kinase C beta