Abstract
Protein phosphorylation is a nearly universal post-translation modification involved in a plethora of cellular events. Even though phosphorylation of extracellular proteins had been observed, the identity of the kinases that phosphorylate secreted proteins remained a mystery until only recently. Advances in genome sequencing and genetic studies have paved the way for the discovery of a new class of kinases that localize within the endoplasmic reticulum, Golgi apparatus and the extracellular space. These novel kinases phosphorylate proteins and proteoglycans in the secretory pathway and appear to regulate various extracellular processes. Mutations in these kinases cause human disease, thus underscoring the biological importance of phosphorylation within the secretory pathway. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases.
Keywords:
Fam20C; Kinases; Raine syndrome; Secretory pathway.
Copyright © 2015 Elsevier B.V. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Review
MeSH terms
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Abnormalities, Multiple / enzymology
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Abnormalities, Multiple / genetics*
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Animals
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Casein Kinase I / chemistry
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Casein Kinase I / genetics*
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Casein Kinase I / metabolism
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Cleft Palate / enzymology
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Cleft Palate / genetics*
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Endoplasmic Reticulum / enzymology
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Endoplasmic Reticulum / genetics
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Exophthalmos / enzymology
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Exophthalmos / genetics*
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Extracellular Matrix Proteins / chemistry
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Extracellular Matrix Proteins / genetics*
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Extracellular Matrix Proteins / metabolism
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Golgi Apparatus / enzymology
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Golgi Apparatus / genetics
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Humans
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Microcephaly / enzymology
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Microcephaly / genetics*
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Mutation
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Osteosclerosis / enzymology
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Osteosclerosis / genetics*
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Phosphorylation / genetics
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Protein Conformation
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Protein-Tyrosine Kinases / chemistry
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Protein-Tyrosine Kinases / genetics*
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Protein-Tyrosine Kinases / metabolism
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Secretory Pathway / genetics*
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Substrate Specificity
Substances
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Extracellular Matrix Proteins
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Protein-Tyrosine Kinases
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PKDCC protein, human
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Casein Kinase I
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FAM20C protein, human