Family with sequence similarity 20, member C (FAM20C) is the main kinase of secreted phosphoproteins, including the multifunctional protein and cytokine, osteopontin (OPN). The phosphorylation of OPN varies greatly among cell types, tissues and species, and the different phospho-isoforms contribute to the multifunctionality of the protein. Expression of OPN is increased in human malignancies, and less phosphorylated isoforms of the protein have been associated with this phenotype. Here, we compared OPN from ras-transformed fibroblasts with that from their non-transformed parental cells, and found that OPN was less phosphorylated after ras-transformation. Furthermore, we demonstrated that expression of FAM20C mRNA was reduced five-fold in ras-transformed fibroblasts compared to non-transformed fibroblasts. Transfection with FAM20C of the ras-transformed fibroblasts restored the FAM20C mRNA expression but the phosphorylation of OPN was not increased proportionally. Likewise, the mRNA level of FAM20C was reduced in the malignant ras-transformed mammary cell line MCF10ACA1a compared to its non-transformed parental cell line MCF10A. These results suggest that expression of the FAM20C kinase is reduced after oncogenic ras-transformation, which potentially affects the phosphorylation of secreted phosphoproteins.

中文翻译：

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Ras 转化减少 FAM20C 表达和骨桥蛋白磷酸化。


具有序列相似性的家族20，成员C（FAM20C）是分泌磷蛋白的主要激酶，包括多功能蛋白和细胞因子骨桥蛋白（OPN）。 OPN 的磷酸化在细胞类型、组织和物种之间存在很大差异，不同的磷酸亚型有助于该蛋白质的多功能性。 OPN 的表达在人类恶性肿瘤中增加，并且该蛋白磷酸化程度较低的亚型与这种表型相关。在这里，我们将 ras 转化的成纤维细胞的 OPN 与其未转化的亲本细胞的 OPN 进行了比较，发现 ras 转化后 OPN 的磷酸化程度较低。此外，我们证明，与未转化的成纤维细胞相比，ras 转化的成纤维细胞中 FAM20C mRNA 的表达降低了五倍。用FAM20C转染ras转化的成纤维细胞可恢复FAM20C mRNA表达，但OPN的磷酸化并未成比例增加。同样，与其未转化的亲代细胞系 MCF10A 相比，恶性 ras 转化的乳腺细胞系 MCF10ACA1a 中 FAM20C 的 mRNA 水平降低。这些结果表明，致癌 ras 转化后 FAM20C 激酶的表达减少，这可能会影响分泌磷蛋白的磷酸化。