Analysis of the catalytic domain of phosphatidylinositol 4-kinase type II

Barbara Barylko, Pawel Wlodarski, Derk D. Binns, Stefan H. Gerber, Svetlana Earnest, Thomas C. Sudhof, Nikolai Grichine, Joseph P. Albanesi

Research output: Contribution to journalArticle

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Abstract

Phosphatidylinositol (PtdIns) 4-kinases catalyze the conversion of PtdIns to PtdIns 4-phosphate, the major precursor of phosphoinositides that regulates a vast array of cellular processes. Based on enzymatic differences, two classes of PtdIns 4-kinase have been distinguished termed Types II and III. Type III kinases, which belong to the phosphatidylinositol (PI) 3/4-kinase family, have been extensively characterized. In contrast, little is known about the Type II enzymes (PI4KIIs), which have been cloned and sequenced very recently. PI4KIIs bear essentially no sequence similarity to other protein or lipid kinases; hence, they represent a novel and distinct branch of the kinase superfamily. Here we define the minimal catalytic domain of a rat PI4KII isoform, PI4KIIα, and identify conserved amino acid residues required for catalysis. We further show that the catalytic domain by itself determines targeting of the kinase to membrane rafts. To verify that the PI4KII family extends beyond mammalian sources, we expressed and characterized Drosophila PI4KII and its catalytic domain. Depletion of PI4KII from Drosophila cells resulted in a severe reduction of PtdIns 4-kinase activity, suggesting the in vivo importance of this enzyme.

Original languageEnglish (US)
Pages (from-to)44366-44375
Number of pages10
JournalJournal of Biological Chemistry
Volume277
Issue number46
DOIs
StatePublished - Nov 15 2002

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1-Phosphatidylinositol 4-Kinase
Catalytic Domain
Phosphotransferases
Phosphatidylinositols
Drosophila
Phosphatidylinositol 3-Kinase
Enzymes
Catalysis
Protein Isoforms
Rats
Lipids
Amino Acids
Membranes
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Analysis of the catalytic domain of phosphatidylinositol 4-kinase type II. / Barylko, Barbara; Wlodarski, Pawel; Binns, Derk D.; Gerber, Stefan H.; Earnest, Svetlana; Sudhof, Thomas C.; Grichine, Nikolai; Albanesi, Joseph P.

In: Journal of Biological Chemistry, Vol. 277, No. 46, 15.11.2002, p. 44366-44375.

Research output: Contribution to journalArticle

Barylko, B, Wlodarski, P, Binns, DD, Gerber, SH, Earnest, S, Sudhof, TC, Grichine, N & Albanesi, JP 2002, 'Analysis of the catalytic domain of phosphatidylinositol 4-kinase type II', Journal of Biological Chemistry, vol. 277, no. 46, pp. 44366-44375. https://doi.org/10.1074/jbc.M203241200
Barylko B, Wlodarski P, Binns DD, Gerber SH, Earnest S, Sudhof TC et al. Analysis of the catalytic domain of phosphatidylinositol 4-kinase type II. Journal of Biological Chemistry. 2002 Nov 15;277(46):44366-44375. https://doi.org/10.1074/jbc.M203241200
Barylko, Barbara ; Wlodarski, Pawel ; Binns, Derk D. ; Gerber, Stefan H. ; Earnest, Svetlana ; Sudhof, Thomas C. ; Grichine, Nikolai ; Albanesi, Joseph P. / Analysis of the catalytic domain of phosphatidylinositol 4-kinase type II. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 46. pp. 44366-44375.
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