Molecular Cloning of Mouse Homologue of Enamel Protein C4orf26 and Its Phosphorylation by FAM20C.
Molecular Cloning of Mouse Homologue of Enamel Protein C4orf26 and Its Phosphorylation by FAM20C.
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DOI：
10.1007/s00223-021-00847-y
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发表时间：
2021-10
影响因子：
4.2
通讯作者：
Mochida Y
中科院分区：
文献类型：
--
作者：
Govitvattana N;Kaku M;Ohyama Y;Jaha H;Lin IP;Mochida H;Pavasant P;Mochida Y
人们普遍认为细胞过程是由蛋白质磷酸化控制的，并且越来越清楚的是，蛋白质降解、定位和构象以及蛋白质-蛋白质相互作用是蛋白质磷酸化调节的后续细胞事件的例子。牙釉质基质蛋白属于聚集在染色体 4q21 上的分泌性钙结合磷蛋白 (SCPP) 家族的成员，大多数 SCPP 磷蛋白具有至少一个 S-X-E 基序（S；丝氨酸，X；任何氨基酸，E；谷氨酸）。据报道，位于染色体 4q21 上的 C4orf26 基因突变与常染色体隐性遗传型釉质生成不全 (AI) 相关，这是一种影响牙釉质形成/矿化的遗传性疾病。在 C4orf26 突变患者中观察到的牙釉质表型矿化不足且部分发育不良，表明 C4orf26 蛋白可能在牙釉质生成的分泌和成熟阶段发挥作用。前期体外研究表明，基于C4orf26蛋白序列合成的磷酸化肽可加速羟基磷灰石成核。在这里，我们展示了 Gm1045 的分子克隆，Gm1045 是 C4orf26 的小鼠同源物，具有 2 个剪接亚型。免疫组织化学分析表明，Gm1045的免疫定位主要在体内观察到的牙釉质基质中。我们的报告首次表明 FAM20C（高尔基体酪蛋白激酶）在细胞培养物中磷酸化 C4orf26 和 Gm1045。 C4orf26/Gm1045 的细胞外定位受 FAM20C 激酶活性调节。因此，我们的数据指出了牙釉质基质激酶控制 SCPP 磷蛋白的生物学重要性，并且可能对釉质生成和 AI 的调节产生广泛的影响。
It is widely accepted that cellular processes are controlled by protein phosphorylation and has become increasingly clear that protein degradation, localization and conformation as well as protein-protein interaction are the examples of subsequent cellular events modulated by protein phosphorylation. Enamel matrix proteins belong to members of the secretory calcium binding phosphoprotein (SCPP) family clustered on chromosome 4q21, and most of the SCPP phosphoproteins have at least one S-X-E motifs (S; serine, X; any amino acid, E; glutamic acid). It has been reported that mutations in C4orf26 gene, located on chromosome 4q21, are associated with autosomal recessive type of Amelogenesis Imperfecta (AI), a hereditary condition that affects enamel formation/mineralization. The enamel phenotype observed in patients with C4orf26 mutations is hypomineralized and partially hypoplastic, indicating that C4orf26 protein may function at both secretory and maturation stages of amelogenesis. The previous in vitro study showed that the synthetic phosphorylated peptide based on C4orf26 protein sequence accelerates hydroxyapatite nucleation. Here we show the molecular cloning of Gm1045, mouse homologue of C4orf26, which has 2 splicing isoforms. Immunohistochemical analysis demonstrated that the immunolocalization of Gm1045 is mainly observed in enamel matrix in vivo. Our report is the first to show that FAM20C, the Golgi casein kinase, phosphorylates C4orf26 and Gm1045 in cell cultures. The extracellular localization of C4orf26/Gm1045 was regulated by FAM20C kinase activity. Thus, our data point out the biological importance of enamel matrix-kinase control of SCPP phosphoproteins and may have a broad impact on the regulation of amelogenesis and AI.
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影响因子：
3.7
作者：
Masica, David L.;Gray, Jeffrey J.;Shaw, Wendy J.
通讯作者：
Shaw, Wendy J.
影响因子：
--
作者：
Acevedo AC;Poulter JA;Alves PG;de Lima CL;Castro LC;Yamaguti PM;Paula LM;Parry DA;Logan CV;Smith CE;Johnson CA;Inglehearn CF;Mighell AJ
通讯作者：
Mighell AJ
影响因子：
3
作者：
Nam, Y;Madapallimattam, G;Bennick, A
通讯作者：
Bennick, A
影响因子：
3
作者：
Collier, PM;Sauk, JJ;Gibson, CW
通讯作者：
Gibson, CW
影响因子：
3
作者：
FINCHAM, AG;HU, Y;SNEAD, ML
通讯作者：
SNEAD, ML