Lipid and peptide control of phosphatidylinositol 4-kinase II alpha activity on Golgi-endosomal rafts

MG Waugh, S Minogue, D Chotai, Fedor Berditchevski, JJ Hsuan

Research output: Contribution to journalArticle

48 Citations (Scopus)


The most abundant and widely expressed mammalian phosphoinositide kinase activity is contributed by phosphatidylinositol 4-kinase II alpha (PI4KII alpha). In this study we demonstrate that PI4KII alpha is a novel GTP-independent target of the wasp venom tetradecapeptide mastoparan and that different mechanisms of activation occur in different subcellular membranes. Following cell membrane fractionation mastoparan specifically stimulated a high activity Golgi/endosomal pool of PI4KII alpha independently of exogenous guanine nucleotides. Conversely, GTP gamma S stimulated a low activity pool of PI4KII alpha in a separable dense membrane fraction and this response was further enhanced by mastoparan. Overexpression of PI4KII alpha increased the basal phosphatidylinositol 4-kinase activity of each membrane pool, as well as the mastoparan-dependent activities, thereby demonstrating that mastoparan specifically activates this isozyme. Both mastoparan and M7, at concentrations known to invoke secretion, stimulated PI4KII alpha with similar efficacies, resulting in an increase in the apparent V-max and decrease in K-m for exogenously added PI. Mastoparan also stimulated PI4KII alpha immunoprecipitated from the raft fraction, indicating that PI4KII alpha is a direct target of mastoparan. Finally we reveal a striking dependence of both basal and mastoparan-stimulated PI4KII alpha activity on endogenous cholesterol concentration and therefore conclude that changes in membrane environment can regulate PI4KII alpha activity.
Original languageEnglish
Pages (from-to)3757-3763
Number of pages7
JournalJournal of Biological Chemistry
Publication statusPublished - 3 Jan 2006


Dive into the research topics of 'Lipid and peptide control of phosphatidylinositol 4-kinase II alpha activity on Golgi-endosomal rafts'. Together they form a unique fingerprint.

Cite this