Biomedical subjects

Robin F Irvine

Publications and source records attributed to Robin F Irvine.

22 records · Page 2Linked to original sources

PubMed2003

Nuclear lipid signalling.

During the past twenty years, evidence has accumulated for the presence of phospholipids within the nuclei of eukaryotic cells. These phospholipids are distinct from those that are obviously present in the nuclear envelope. The best characterized of the intranuclear lipids are the inositol lipids that form the components of a phosphoinositide-phospholipase C cycle. However, exactly as has been discovered in the cytoplasm, this is just part of a complex picture that involves many other lipids and functions.

1-Phosphatidylinositol 4-Kinase↗

PubMed2003

20 years of Ins(1,4,5)P3, and 40 years before.

This year marks the 20th birthday of the discovery of inositol-1,4,5-trisphosphate as a second messenger. The background to this discovery is a complex story that goes back more than 50 years and involves a large cast of characters, both chemical and human.

History, 20th Century↗

PubMed2002

Nuclear lipid signaling.

Abundant evidence now supports the existence of phospholipids in the nucleus that resist washing of nuclei with detergents. These lipids are apparently not in the nuclear envelope as part of a bilayer membrane, but are actually within the nucleus in the form of proteolipid complexes with unidentified proteins. This review discusses the experimental evidence that attempts to explain their existence. Among these nuclear lipids are the polyphosphoinositol lipids which, together with the enzymes that synthesize them, form an intranuclear phospholipase C (PI-PLC) signaling system that generates diacylglycerol (DAG) and inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. The isoforms of PI-PLC that are involved in this signaling system, and how they are regulated, are not yet entirely clear. Generation of DAG within the nucleus is believed to recruit protein kinase C (PKC) to the nucleus to phosphorylate intranuclear proteins. Generation of Ins(1,4,5)P3 may mobilize Ca2+ from the space between the nuclear membranes and thus increase nucleoplasmic Ca2+. Less well understood are the increasing number of variations and complications on the "simple" idea of a PI-PLC system. These include, all apparently within the nucleus, (i) two routes of synthesis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2]; (ii) two sources of DAG, one from the PI-PLC pathway and the other probably from phosphatidylcholine; (iii) several isoforms of PKC translocating to nuclei; (iv) increases in activity of the PI-PLC pathway at two points in the cell cycle; (v) a pathway of phosphorylation of Ins(1,4,5)P3, which may have several functions, including a role in the transfer of mRNA out of the nucleus; and (vi) the possible existence of other lipid signaling pathways that may include sphingolipids, phospholipase A2, and, in particular, 3-phosphorylated inositol lipids, which are now emerging as possible major players in nuclear signaling.

Animals↗

PubMed2002

Type IIalpha phosphatidylinositol phosphate kinase associates with the plasma membrane via interaction with type I isoforms.

The phosphatidylinositol phosphate kinases (PIPkins) are a family of enzymes involved in regulating levels of several functionally important inositol phospholipids within cells. The PIPkin family is subdivided into three on the basis of substrate specificity, each subtype presumably regulating levels of different subsets of the inositol lipids. The physiological function of the type II isoforms, which exhibit a preference for phosphatidylinositol 5-phosphate, a lipid about which very little is known, is particularly poorly understood. In the present study, we demonstrate interaction between, and co-immunoprecipitation of, type IIalpha PIPkin with the related, but biochemically and immunologically distinct, type I PIPkin isoforms. Type IIalpha PIPkin interacts with all three known type I PIPkins (alpha, beta and gamma), and in each case co-expression of the type I isoform with type IIalpha results in recruitment of the latter from the cytosol to the plasma membrane of the cell. This change in subcellular localization could result in improved access of the type IIalpha PIPkin to its lipid substrates.

Animals↗