A secretory kinase complex regulates extracellular protein phosphorylation
- University of California, San Diego, United States
- Peking University, China
- Merck & Co, United States
- ISIS Pharmaceuticals, United States
Abstract
Although numerous extracellular phosphoproteins have been identified, the protein kinases within the secretory pathway have only recently been discovered, and their regulation is virtually unexplored. Fam20C is the physiological Golgi casein kinase, which phosphorylates many secreted proteins and is critical for proper biomineralization. Fam20A, a Fam20C paralog, is essential for enamel formation, but the biochemical function of Fam20A is unknown. Here we show that Fam20A potentiates Fam20C kinase activity and promotes the phosphorylation of enamel matrix proteins in vitro and in cells. Mechanistically, Fam20A is a pseudokinase that forms a functional complex with Fam20C, and this complex enhances extracellular protein phosphorylation within the secretory pathway. Our findings shed light on the molecular mechanism by which Fam20C and Fam20A collaborate to control enamel formation, and provide the first insight into the regulation of secretory pathway phosphorylation.
Article and author information
Author details
Reviewing Editor
- Tony Hunter, Salk Institute, United States
Ethics
Animal experimentation: Procedures involving mice were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) at the UC San Diego (Protocol #S03039).
Version history
- Received: December 16, 2014
- Accepted: March 18, 2015
- Accepted Manuscript published: March 19, 2015 (version 1)
- Version of Record published: May 6, 2015 (version 2)
Copyright
© 2015, Cui et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A secretory kinase complex regulates extracellular protein phosphorylation
eLife 4:e06120.
https://doi.org/10.7554/eLife.06120
Further reading
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- Biochemistry and Chemical Biology
The interaction between an active kinase and an ‘inactive’ pseudokinase provides clues about how these enzymes were regulated in the past, and how this regulation has evolved.
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- Biochemistry and Chemical Biology
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