A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate
- PMID: 9367159
- DOI: 10.1038/36621
A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate
Abstract
Phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2), a key molecule in the phosphoinositide signalling pathway, was thought to be synthesized exclusively by phosphorylation of PtdIns-4-P at the D-5 position of the inositol ring. The enzymes that produce PtdIns-4,5-P2 in vitro fall into two related subfamilies (type I and type II PtdInsP-5-OH kinases, or PIP(5)Ks) based on their enzymatic properties and sequence similarities'. Here we have reinvestigated the substrate specificities of these enzymes. As expected, the type I enzyme phosphorylates PtdIns-4-P at the D-5 position of the inositol ring. Surprisingly, the type II enzyme, which is abundant in some tissues, phosphorylates PtdIns-5-P at the D-4 position, and thus should be considered as a 4-OH kinase, or PIP(4)K. The earlier error in characterizing the activity of the type II enzyme is due to the presence of contaminating PtdIns-5-P in commercial preparations of PtdIns-4-P. Although PtdIns-5-P was previously thought not to exist in vivo, we find evidence for the presence of this lipid in mammalian fibroblasts, establishing a new pathway for PtdIns-4,5-P2 synthesis.
Comment in
-
Inositol lipid pathways turn turtle.Nature. 1997 Nov 13;390(6656):123-4. doi: 10.1038/36458. Nature. 1997. PMID: 9367149 No abstract available.
Similar articles
-
Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate.Nature. 1988 Apr 14;332(6165):644-6. doi: 10.1038/332644a0. Nature. 1988. PMID: 2833705
-
Phosphatidylinositol Kinases and Phosphatases in Entamoeba histolytica.Front Cell Infect Microbiol. 2019 Jun 6;9:150. doi: 10.3389/fcimb.2019.00150. eCollection 2019. Front Cell Infect Microbiol. 2019. PMID: 31245297 Free PMC article. Review.
-
Phosphatidylinositol 3,4,5-trisphosphate is a substrate for the 75 kDa inositol polyphosphate 5-phosphatase and a novel 5-phosphatase which forms a complex with the p85/p110 form of phosphoinositide 3-kinase.EMBO J. 1995 Sep 15;14(18):4490-500. doi: 10.1002/j.1460-2075.1995.tb00128.x. EMBO J. 1995. PMID: 7556092 Free PMC article.
-
Phosphoinositide 3-phosphatase segregates from phosphatidylinositol 3-kinase in EGF-stimulated A431 cells and fails to in vitro hydrolyse phosphatidylinositol(3,4,5)trisphosphate.FEBS Lett. 1994 Mar 14;341(1):113-8. doi: 10.1016/0014-5793(94)80251-3. FEBS Lett. 1994. PMID: 8137909
-
Type II PtdInsP kinases: location, regulation and function.Biochem Soc Symp. 2007;(74):149-59. doi: 10.1042/BSS0740149. Biochem Soc Symp. 2007. PMID: 17233588 Review.
Cited by
-
Nuclear phosphatidylinositol-5-phosphate regulates ING2 stability at discrete chromatin targets in response to DNA damage.Sci Rep. 2013;3:2137. doi: 10.1038/srep02137. Sci Rep. 2013. PMID: 23823870 Free PMC article.
-
Mechanism of substrate specificity of phosphatidylinositol phosphate kinases.Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):8711-6. doi: 10.1073/pnas.1522112113. Epub 2016 Jul 20. Proc Natl Acad Sci U S A. 2016. PMID: 27439870 Free PMC article.
-
Learning-related synaptic growth mediated by internalization of Aplysia cell adhesion molecule is controlled by membrane phosphatidylinositol 4,5-bisphosphate synthetic pathway.J Neurosci. 2012 Nov 14;32(46):16296-305. doi: 10.1523/JNEUROSCI.1872-12.2012. J Neurosci. 2012. PMID: 23152613 Free PMC article.
-
Regulation of eukaryotic protein kinases by Pin1, a peptidyl-prolyl isomerase.Adv Biol Regul. 2023 Jan;87:100938. doi: 10.1016/j.jbior.2022.100938. Epub 2022 Nov 30. Adv Biol Regul. 2023. PMID: 36496344 Free PMC article.
-
A novel HPLC-based approach makes possible the spatial characterization of cellular PtdIns5P and other phosphoinositides.Biochem J. 2010 May 27;428(3):375-84. doi: 10.1042/BJ20100129. Biochem J. 2010. PMID: 20370717 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials