National Centre for Biological Sciences, TIFR-GKVK Campus, Bellary Road, Bangalore 560065, India.
School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India.
Biosci Rep. 2019 Feb 19;39(2). doi: 10.1042/BSR20182210. Print 2019 Feb 28.
Phosphatidylinositol 5 phosphate 4-kinase (PIP4K) are enzymes that catalyse the phosphorylation of phosphatidylinositol 5-phosphate (PI5P) to generate PI(4,5)P Mammalian genomes contain three genes, and and murine knockouts for these suggested important physiological roles The proteins encoded by and show widely varying specific activities ; PIP4K2A is highly active and PIP4K2C 2000-times less active, and the relationship between this biochemical activity and function is unknown. By contrast, the genome encodes a single PIP4K (dPIP4K) that shows high specific activity and loss of this enzyme results in reduced salivary gland cell size We find that the kinase activity of dPIP4K is essential for normal salivary gland cell size Despite their highly divergent specific activity, we find that all three mammalian PIP4K isoforms are able to enhance salivary gland cell size in the PIP4K null mutant implying a lack of correlation between activity measurements and function. Further, the kinase activity of PIP4K2C, reported to be almost inactive , is required for function. Our findings suggest the existence of unidentified factors that regulate PIP4K enzyme activity .
磷酸肌醇 5 磷酸 4-激酶 (PIP4K) 是催化磷酸肌醇 5-磷酸 (PI5P) 磷酸化生成 PI(4,5)P 的酶。哺乳动物基因组包含三个基因，和，这些基因的敲除提示它们具有重要的生理作用。由和编码的蛋白质显示出广泛不同的比活性；PIP4K2A 具有很高的活性，而 PIP4K2C 的活性则低 2000 倍，这种生化活性与功能之间的关系尚不清楚。相比之下，基因组编码单个 PIP4K (dPIP4K)，具有很高的比活性，该酶的缺失导致唾液腺细胞体积减小。我们发现 dPIP4K 的激酶活性对于正常的唾液腺细胞大小是必需的。尽管它们的比活性高度不同，但我们发现所有三种哺乳动物 PIP4K 同工型都能够增强在 PIP4K 缺失突变体中的唾液腺细胞大小，这表明活性测量与功能之间缺乏相关性。此外，报道活性几乎无活性的 PIP4K2C 的激酶活性对于功能是必需的。我们的发现表明存在调节 PIP4K 酶活性的未识别因子。
