2015
DOI: 10.1016/j.cell.2015.05.028
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A Single Kinase Generates the Majority of the Secreted Phosphoproteome

Abstract: Summary The existence of extracellular phosphoproteins has been acknowledged for over a century. However, research in this area has been undeveloped largely because the kinases that phosphorylate secreted proteins have escaped identification. Fam20C is a kinase that phosphorylates S-x-E/pS motifs on proteins in milk and in the extracellular matrix of bones and teeth. Here, we show that Fam20C generates the majority of the extracellular phosphoproteome. Using CRISPR/Cas9 genome editing, mass spectrometry, and b… Show more

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Cited by 290 publications
(386 citation statements)
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“…Indeed, FAM20C is a kinase that phosphorylates the majority of the phosphoproteome in the extracellular matrices of bones and teeth, constituting a key player in vertebrate biomineralization processes [66]. Other recent investigations have revealed the presence of FAM20C-containing protein in the shell matrix of the giant limpet Lottia gigantea [48] and of the brachiopod Magellania venosa [58].…”
Section: Are Metazoan Shell Matrix Proteins Deeply Conserved?mentioning
confidence: 99%
“…Indeed, FAM20C is a kinase that phosphorylates the majority of the phosphoproteome in the extracellular matrices of bones and teeth, constituting a key player in vertebrate biomineralization processes [66]. Other recent investigations have revealed the presence of FAM20C-containing protein in the shell matrix of the giant limpet Lottia gigantea [48] and of the brachiopod Magellania venosa [58].…”
Section: Are Metazoan Shell Matrix Proteins Deeply Conserved?mentioning
confidence: 99%
“…Phosphosite mapping of insulin-like growth factor-binding protein 1 in vitro phosphorylated by Fam20C also indicated modifications in non Ser-Xxx-Glu/ pSer motives. The authors speculated that the recognition motif of Fam20C might be significantly broader than originally suspected, however, kinase assays performed with synthetic peptides could extend Fam20C activity only to Ser-Xxx-GlnXxx-Xxx-Asp/Glu-Asp/Glu-Asp/Glu sequences present in proline-rich phosphoprotein 1 (PRP1) (7,23). In addition, one has to consider the potential existence of "phosphorylation cascades" in the Golgi where the elimination of a kinase affects not only the direct substrates but also all the "downstream" modifications.…”
mentioning
confidence: 99%
“…It resides in the Golgi but it can also be found in an N-terminally truncated, secreted form (6, 7). Phosphorylation of the substrate proteins occurs intracellularly (7,8), yet Fam20C may exert its activity also extracellularly. Fam20C was demonstrated to phosphorylate a wide array of secreted proteins involved in biomineralization, lipid homeostasis, wound healing, cell adhesion, and migration (7).…”
mentioning
confidence: 99%
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“…Fam20C, the most celebrated member of this unconventional kinase cohort, turns out to be the physiological casein kinase. This enzyme plays a key regulatory role in the maturation of the milk protein casein, and human mutations in Fam20C are linked to Raine syndrome, a deadly osteosclerotic bone dysplasia (10). However, the link between Fam20C-like kinases and bacterial spore coat proteins had yet to be made.…”
mentioning
confidence: 99%