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J Biol Chem, Vol. 273, Issue 11, 6001-6004, March 13, 1998
COMMUNICATION
Regulation of Aquaporin-4 Water Channels by Phorbol
Ester-dependent Protein Phosphorylation
Zhiqiang
Han,
Martin B.
Wax, and
Rajkumar V.
Patil
From the Department of Ophthalmology and Visual Sciences,
Washington University School of Medicine,
St. Louis, Missouri 63110
The molecular mechanisms for regulating water
balance in many tissues are unknown. Like the kidney, the eye contains
multiple water channel proteins (aquaporins) that transport water
through membranes, including two (AQP1 and AQP4) in the ciliary body, the site of aqueous humor production. However, because humans with
defective AQP1 are phenotypically normal and because the ocular
application of phorbol esters reduce intraocular pressure, we
postulated that the water channel activity of AQP4 may be regulated by
these agents. We now report that protein kinase C activators, phorbol
12,13-dibutyrate, and phorbol 12-myristate 13-acetate strongly
stimulate the phosphorylation of AQP4 and inhibit its activity in a
dose-dependent manner. Phorbol 12,13-dibutyrate (10 µM) and phorbol 12-myristate 13-acetate (10 nM) reduced the rate of AQP4-expressing oocyte swelling by
87 and 92%, respectively. Further, phorbol 12,13-dibutyrate
significantly increased the amount of phosphorylated AQP4. These
results demonstrate that protein kinase C can regulate the activity of
AQP4 through a mechanism involving protein phosphorylation. Moreover,
they suggest important potential roles for AQP4 in several clinical
disorders involving rapid water transport such as glaucoma, brain
edema, and swelling of premature infant lungs.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 1998 by the American Society for Biochemistry and Molecular Biology.
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