Regulation of Ins(3,4,5,6)P-4 signaling by a reversible kinase/phosphatase
SCIE
SCOPUS
- Title
- Regulation of Ins(3,4,5,6)P-4 signaling by a reversible kinase/phosphatase
- Authors
- Ho, MWY; Yang, XN; Carew, MA; Zhang, T; Hua, L; Kwon, YU; Chung, SK; Adelt, S; Vogel, G; Riley, AM; Potter, BVL; Shears, SB
- Date Issued
- 2002-03-19
- Publisher
- CELL PRESS
- Abstract
- Regulation of Cl- channel conductance by Ins(3,4,5,6)P-4 provides receptor-dependent control over salt and fluid secretion [1], cell volume homeostasis [2], and electrical excitability of neurones and smooth muscle [3]. Ignorance of how Ins(3,4,5,6)P4 is synthesized has long hindered our understanding of this signaling pathway. We now show Ins(3,4,5,6)P4 synthesis by Ins(1,3,4,5,6)P,5 1-phosphatase activity by an enzyme previously characterized [4] as an Ins(3,4,5,6)P-4 1-kinase. Rationalization of these phenomena with a ligand binding model unveils Ins(1,3,4)P-3 as not simply an alternative kinase substrate [4, 5], but also an activator of Ins(1,3,4,5,6)P-5 I-phosphatase. Stable overexpression of the enzyme in epithelial monolayers verifies its physiological role in elevating Ins(3,4,5,6)P4 levels and inhibiting secretion. It is exceptional for a single enzyme to catalyze two opposing signaling reactions (1-kinase/1-phosphatase) under physiological conditions. Reciprocal coordination of these opposing reactions offers an alternative to general doctrine that intracellular signals are regulated by integrating multiple, distinct phosphatases and kinases [6].
- Keywords
- D-MYO-INOSITOL; MYOINOSITOL 3,4,5,6-TETRAKISPHOSPHATE; RAT-LIVER; ENZYME; 1,3,4-TRISPHOSPHATE; TETRAKISPHOSPHATES; HEXAKISPHOSPHATE; 5/6-KINASE; CELLS
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/19154
- DOI
- 10.1016/S0960-9822(02)00713-3
- ISSN
- 0960-9822
- Article Type
- Article
- Citation
- CURRENT BIOLOGY, vol. 12, no. 6, page. 477 - 482, 2002-03-19
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- There are no files associated with this item.
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