Presence and Activation of Nuclear Phosphoinositide 3-Kinase C2β during Compensatory Liver Growth

Aleksandra Sindić, Aleksandra Aleksandrova, Alan P. Fields, Stefano Volinia, Hrvoje Banfić

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Highly purified liver nuclei incorporated radiolabeled phosphate into phosphatidylinositol 4-phosphate (PtdIns(4)P), PtdIns(4,5)P2, and PtdIns(3,4,5)P3. When nuclei were depleted of their membrane, no radiolabeling of PtdIns(3,4,5)P3 could be detected showing that within the intranuclear region there are no class I phosphoinositide 3-kinases (PI3K)s. In membrane-depleted nuclei harvested 20 h after partial hepatectomy, the incorporation of radiolabel into PtdIns(3)P was observed together with an increase in immunoprecipitable PI3K-C2β activity, which is sensitive to wortmannin (10 nM) and shows strong preference for PtdIns over PtdIns(4)P as a substrate. On Western blots PI3K-C2β revealed a single immunoreactive band of 180 kDa, whereas 20 h after partial hepatectomy gel shift of 18 kDa was noticed, suggesting that observed activation of enzyme is achieved by proteolysis. When intact membrane-depleted nuclei were subjected to short term (20 min) exposure to μ-calpain, similar gel shift together with an increase in PI3K-C2β activity was observed, when compared with the nuclei harvested 20 h after partial hepatectomy. Moreover, the above-mentioned gel shift and increase in PI3K-C2β activity could be prevented by the calpain inhibitor calpeptin. The data presented in this report show that, in the membrane-depleted nuclei during the compensatory liver growth, there is an increase in PtdIns(3)P formation as a result of PI3K-C2β activation, which may be a calpain-mediated event.

Original languageEnglish (US)
Pages (from-to)17754-17761
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number21
DOIs
StatePublished - Jan 25 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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