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Lipid-independent activation of a muscle-specific PKCα splicing variant.

Publication ,  Journal Article
Gao, C; Gong, J; Cao, N; Wang, Y; Steinberg, SF
Published in: Am J Physiol Heart Circ Physiol
October 1, 2022

Protein kinase C-α (PKCα) plays a major role in a diverse range of cellular processes. Studies to date have defined the regulatory controls and function of PKCα entirely based upon the previously annotated ubiquitously expressed prototypical isoform. From RNA-seq-based transcriptome analysis in murine heart, we identified a previously unannotated PKCα variant produced by alternative RNA splicing. This PKCα transcript variant, which we named PKCα-novel exon (PKCα-NE), contains an extra exon between exon 16 and exon 17, and is specifically detected in adult mouse cardiac and skeletal muscle, but not other tissues; it is also detected in human hearts. This transcript variant yields a PKCα isoform with additional 16 amino acids inserted in its COOH-terminal variable region. Although the canonical PKCα enzyme is a lipid-dependent kinase, in vitro kinase assays show that PKCα-NE displays a high level of basal lipid-independent catalytic activity. Our unbiased proteomic analysis identified a specific interaction between PKCα-NE and eukaryotic elongation factor-1α (eEF1A1). Studies in cardiomyocytes link PKCα-NE expression to an increase in eEF1A1 phosphorylation and elevated protein synthesis. In summary, we have identified a previously uncharacterized muscle-specific PKCα splicing variant, PKCα-NE, with distinct biochemical properties that plays a unique role in the control of the protein synthesis machinery in cardiomyocytes.NEW & NOTEWORTHY PKCα is an important signaling molecule extensively studied in many cellular processes. However, no isoforms have been reported for PKCα except one prototypic isoform. Alternative mRNA splicing of Prkca gene was detected for the first time in rodent and human cardiac tissue, which can produce a previously unknown PKCα-novel exon (NE) isoform. The biochemistry and molecular effects of PKCα-NE are markedly different from PKCα wild type, suggesting potential functional diversity of PKCα signaling in muscle.

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Published In

Am J Physiol Heart Circ Physiol

DOI

EISSN

1522-1539

Publication Date

October 1, 2022

Volume

323

Issue

4

Start / End Page

H825 / H832

Location

United States

Related Subject Headings

  • RNA, Messenger
  • Proteomics
  • Protein Kinase C-alpha
  • Protein Isoforms
  • Myocytes, Cardiac
  • Muscle, Skeletal
  • Mice
  • Lipids
  • Humans
  • Cardiovascular System & Hematology
 

Citation

APA
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Gao, C., Gong, J., Cao, N., Wang, Y., & Steinberg, S. F. (2022). Lipid-independent activation of a muscle-specific PKCα splicing variant. Am J Physiol Heart Circ Physiol, 323(4), H825–H832. https://doi.org/10.1152/ajpheart.00304.2022
Gao, Chen, Jianli Gong, Nancy Cao, Yibin Wang, and Susan F. Steinberg. “Lipid-independent activation of a muscle-specific PKCα splicing variant.Am J Physiol Heart Circ Physiol 323, no. 4 (October 1, 2022): H825–32. https://doi.org/10.1152/ajpheart.00304.2022.
Gao C, Gong J, Cao N, Wang Y, Steinberg SF. Lipid-independent activation of a muscle-specific PKCα splicing variant. Am J Physiol Heart Circ Physiol. 2022 Oct 1;323(4):H825–32.
Gao, Chen, et al. “Lipid-independent activation of a muscle-specific PKCα splicing variant.Am J Physiol Heart Circ Physiol, vol. 323, no. 4, Oct. 2022, pp. H825–32. Pubmed, doi:10.1152/ajpheart.00304.2022.
Gao C, Gong J, Cao N, Wang Y, Steinberg SF. Lipid-independent activation of a muscle-specific PKCα splicing variant. Am J Physiol Heart Circ Physiol. 2022 Oct 1;323(4):H825–H832.

Published In

Am J Physiol Heart Circ Physiol

DOI

EISSN

1522-1539

Publication Date

October 1, 2022

Volume

323

Issue

4

Start / End Page

H825 / H832

Location

United States

Related Subject Headings

  • RNA, Messenger
  • Proteomics
  • Protein Kinase C-alpha
  • Protein Isoforms
  • Myocytes, Cardiac
  • Muscle, Skeletal
  • Mice
  • Lipids
  • Humans
  • Cardiovascular System & Hematology