The A-kinase anchoring protein b-synemin binds PKCe

FASEB JOURNAL(2019)

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Abstract
Synemin is a type IV intermediate filament (IF) protein. The two largest isoforms (α and β) are co‐expressed in a variety of cell types including muscle cells. Earlier we found that in muscle cells α‐synemin preferentially localizes to the sarcolemma and intercalated disks while β‐synemin is concentrated at the Z‐disks. Both isoforms also have an unusually long tail domain compared to most IF proteins. This domain is a site for numerous protein interactions, some unique to each isoform and some common to both. For example, in the past we found that both bind protein kinase A (PKA) and are thus also classified as A‐kinase anchoring proteins (AKAPs). AKAPs act to tether PKA to specific subcellular locations to maintain the specificity of the PKA signaling pathway. Excitingly, we have now found evidence that synemin also binds PKCɛ. Specifically, co‐immunoprecipitation studies show that PKCɛ binds to β‐synemin only upon stimulation of the β‐adrenergic pathway with isoproterenol. Additionally, western analysis using cells expressing either wild type or mutant β‐synemin indicates that, upon loss of β‐synemin anchored PKA, there is a decrease in phosphorylation of PKC substrates, including a ~22 kDa protein. Studies are ongoing to determine the identity of this protein. Based on molecular weight and known PKCɛ substrates in muscle cells we predict this protein is either troponin I (TnI) or myosin regulatory light chain 2 (RLC2). In support of RLC2, yeast‐two hybrid analysis revealed that protein‐protein interaction occurs between β‐synemin and RLC2. Thus, β‐synemin is proposed be a site of cross‐talk between PKA and PKCɛ and also may localize these kinases to the sarcomere at the substrate for PKCɛ. Support or Funding Information NIH R01 HL65701 (DD) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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Key words
a‐kinase,protein
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