Original Paper

Histochemistry and Cell Biology

, Volume 121, Issue 4, pp 343-350

First online:

Juxtamembrane localization of the protein phosphatase-1 inhibitor protein PHI-1 in smooth muscle cells

  • Nikolaos A. TountasAffiliated withCenter for Cell Signaling, University of Virginia School of Medicine
  • , James W. MandellAffiliated withDepartment of Pathology (Neuropathology), University of Virginia Health System
  • , Allen D. EverettAffiliated withDepartment of Pediatrics and the Cardiovascular Research Center, University of Virginia Health SystemDepartment of Pediatrics, Johns Hopkins School of Medicine
  • , David L. BrautiganAffiliated withCenter for Cell Signaling, University of Virginia School of Medicine Email author 

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Abstract

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.

Keywords

CPI-17 Intestine Endothelium Heart Immunohistochemistry