Regulation of aquaporin-4 water channels by phorbol ester-dependent protein phosphorylation

Zhiqiang Han, Martin B. Wax, Rajkumar V. Patil

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6001-6004
Number of pages4
JournalJournal of Biological Chemistry
Volume273
Issue number11
DOIs
StatePublished - Mar 13 1998

Fingerprint

Aquaporin 4
Phorbol 12,13-Dibutyrate
Aquaporins
Phosphorylation
Phorbol Esters
Brain Edema
Protein Kinase C
Swelling
Water
Acetates
Ciliary Body
Proteins
Aqueous Humor
Protein Transport
Intraocular Pressure
Premature Infants
Glaucoma
Oocytes
Brain
Tissue

ASJC Scopus subject areas

  • Biochemistry

Cite this

Regulation of aquaporin-4 water channels by phorbol ester-dependent protein phosphorylation. / Han, Zhiqiang; Wax, Martin B.; Patil, Rajkumar V.

In: Journal of Biological Chemistry, Vol. 273, No. 11, 13.03.1998, p. 6001-6004.

Research output: Contribution to journalArticle

Han, Zhiqiang ; Wax, Martin B. ; Patil, Rajkumar V. / Regulation of aquaporin-4 water channels by phorbol ester-dependent protein phosphorylation. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 11. pp. 6001-6004.
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