The Raine syndrome protein FAM20C is a Golgi kinase that phosphorylates bio-mineralization proteins.
The Raine syndrome protein FAM20C is a Golgi kinase that phosphorylates bio-mineralization proteins.
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DOI：
10.1371/journal.pone.0042988
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Irvine KD
中科院分区：
文献类型：
--
作者：
Ishikawa HO;Xu A;Ogura E;Manning G;Irvine KD
雷恩综合征是由FAM20C突变引起的，据报道，FAM20C编码骨骼和牙齿的分泌成分。我们发现FAM20C编码一个高尔基定位蛋白激酶，与高尔基定位激酶四关节有远亲关系。果蝇也编码与FAM20C密切相关的高尔基定位蛋白激酶。我们发现FAM20C可以磷酸化分泌的磷酸化蛋白，包括酪蛋白和兄弟蛋白家族的成员，这些蛋白调节生物矿化，我们发现FAM20C磷酸化了抑制生物矿化所必需的氨基酸上的生物活性肽。我们还鉴定了FAM20C的自磷酸化，并表征了FAM20C激酶活性的参数，包括其Km、pH和阳离子依赖性以及底物特异性。FAM20C的生化特性与高尔基酪蛋白激酶的酶活性相匹配。将Raine综合征患者中发现的点突变引入重组FAM20C，会损害其正常定位和激酶活性。我们的研究结果确定FAM20C是分泌磷蛋白的激酶，并建立了Raine综合征的生化基础。
Raine syndrome is caused by mutations in FAM20C, which had been reported to encode a secreted component of bone and teeth. We found that FAM20C encodes a Golgi-localized protein kinase, distantly related to the Golgi-localized kinase Four-jointed. Drosophila also encode a Golgi-localized protein kinase closely related to FAM20C. We show that FAM20C can phosphorylate secreted phosphoproteins, including both Casein and members of the SIBLING protein family, which modulate biomineralization, and we find that FAM20C phosphorylates a biologically active peptide at amino acids essential for inhibition of biomineralization. We also identify autophosphorylation of FAM20C, and characterize parameters of FAM20C’s kinase activity, including its Km, pH and cation dependence, and substrate specificity. The biochemical properties of FAM20C match those of an enzymatic activity known as Golgi casein kinase. Introduction of point mutations identified in Raine syndrome patients into recombinant FAM20C impairs its normal localization and kinase activity. Our results identify FAM20C as a kinase for secreted phosphoproteins and establish a biochemical basis for Raine syndrome.
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影响因子：
6.2
作者：
Deshpande, Atul Suresh;Fang, Ping-An;Zhang, Xiaoyuan;Jayaraman, Thottala;Sfeir, Charles;Beniash, Elia
通讯作者：
Beniash, Elia
四关节是一种高尔基激酶，可磷酸化钙粘蛋白结构域的子集。
影响因子：
56.9
作者：
Ishikawa, Hiroyuki O.;Takeuchi, Hideyuki;Haltiwanger, Robert S.;Irvine, Kenneth D.
通讯作者：
Irvine, Kenneth D.
DOI：
10.1186/1745-7580-4-5
发表时间：
2008-04-29
期刊：
Immunome research
影响因子：
--
作者：
Lattin JE;Schroder K;Su AI;Walker JR;Zhang J;Wiltshire T;Saijo K;Glass CK;Hume DA;Kellie S;Sweet MJ
通讯作者：
Sweet MJ
影响因子：
2
作者：
Mann, Karlheinz;Poustka, Albert J.;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
4.2
作者：
Gericke, A;Qin, C;Boskey, AL
通讯作者：
Boskey, AL