Agonist Activated PKC beta(II) Translocation and Modulation of Cardiac Myocyte Contractile Function

作者：Hwang Hyosook^*; Robinson Dustin; Rogers Julie B; Stevenson Tamara K; Lang Sarah E; Sadayappan Sakthivel; Day Sharlene M; Sivaramakrishnan Sivaraj; Westfall Margaret V

来源：Scientific Reports, 2013, 3(1): 1971.

DOI：10.1038/srep01971

Elevated protein kinase C beta(II) (PKC beta(II)) 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 PKC beta(II) activation on contractile function in adult cardiacmyocytes. Diminished contractile function develops in response to low dose phenylephrine (PHE, 100 nM) in controls, while function is preserved in response to PHE in PKC beta(II)-expressing myocytes. PHE also caused PKC beta(II) 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 PKC beta(II)-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 PKC beta(II)-expressing myocytes. These patterns are consistent with bifurcated activation of downstream signaling activity by PKC beta(II).

• 出版日期2013-6-12