Tountas Nikolaos A, Mandell James W, Everett Allen D, Brautigan David L
Center for Cell Signaling, University of Virginia School of Medicine, PO Box 800577, Charlottesville, VA 22908, USA.
Histochem Cell Biol. 2004 Apr;121(4):343-50. doi: 10.1007/s00418-004-0642-8. Epub 2004 Apr 9.
Protein phosphorylation regulates many fundamental processes and protein phosphatase-1 (PP1) is a major phosphatase that determines the levels of Ser/Thr phosphorylation. Regulatory subunits and inhibitor phosphoproteins control PP1 activity. PHI-1 is a member of a family of PP1 inhibitor phosphoproteins that was discovered based on sequence similarity to the known inhibitor CPI-17. To learn more about PHI-1 we determined the tissue distribution of PHI-1 in embryonic and adult tissues, and examined its cellular localization by immunohistochemistry. In the embryo PHI-1 appeared first in the heart at E10, and by E15 it was detected in multiple tissues. Expression in adult tissues was strikingly different, with PHI-1 detected primarily in smooth muscles in the intestine, blood vessels, and male and female genitourinary tracts. PHI-1 also was highly expressed in the endothelial layer of blood vessels. Both PHI-1 and CPI-17 are expressed predominantly in adult smooth muscles. Whereas CPI-17 staining was diffuse PHI-1 was concentrated along the cell membrane in distinct foci, detected by confocal and electron microscopy. The common tissue distribution but different cellular localization of PHI-1 and CPI-17 suggest distinctive physiological roles for these two PP1 inhibitors.
蛋白质磷酸化调节许多基本过程，蛋白磷酸酶-1（PP1）是一种主要的磷酸酶，它决定丝氨酸/苏氨酸磷酸化水平。调节亚基和抑制性磷蛋白控制PP1的活性。PHI-1是PP1抑制性磷蛋白家族的一员，它是基于与已知抑制剂CPI-17的序列相似性而被发现的。为了更多地了解PHI-1，我们确定了PHI-1在胚胎和成年组织中的组织分布，并通过免疫组织化学检查了其细胞定位。在胚胎中，PHI-1在E10时首先出现在心脏，到E15时在多个组织中被检测到。在成年组织中的表达明显不同，PHI-1主要在肠道、血管以及男性和女性泌尿生殖道的平滑肌中被检测到。PHI-1在血管内皮细胞层中也高度表达。PHI-1和CPI-17都主要在成年平滑肌中表达。通过共聚焦显微镜和电子显微镜检测发现，CPI-17染色呈弥漫性，而PHI-1则集中在细胞膜上的不同病灶处。PHI-1和CPI-17共同的组织分布但不同的细胞定位表明这两种PP1抑制剂具有独特的生理作用。
