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. 2019 Jun 30;20(13):3219. doi: 10.3390/ijms20133219

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© 2019 by the author.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Model of Class IIa HDAC Kinase Phosphorylation by SIK1. An increase in Na⁺_in results in an increase in Ca²⁺_in due to activation of Na⁺/Ca²⁺ exchange activity. SIK1 is phosphorylated at Thr322 by CAMK1 and activated, resulting in the phosphorylation of Class IIa HDACs associated with MEF2 transcriptions (as well as NFAT, not shown) on chromosomal DNA. As a consequence of their phosphorylation at two sites (Ser259 and Ser498 in the case of Human HDAC5), Class IIa HDACS translocate to the cytoplasm where they interact with 14-3-3 proteins. If the indicated reaction has a positive effect upon activity, it is indicated by a plus contained within a circle.