Bacterial lipopolysaccharide (LPS) induces strong pro-inflammatory reactions after sequential binding to CD14 protein and TLR4 receptor. Here, we show that CD14 controls generation of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] in response to LPS binding. In J774 cells and HEK293 cells expressing CD14 exposed to 10-100 ng/ml LPS, the level of PI(4,5)P2 rose in a biphasic manner with peaks...

In a previous study we demonstrated that antiviral response against the coliphage MS-2 can be elicited by immunization with a synthetic antigen consisting of a conjugate (P2-A -- L) of a synthetic fragment (P2) of the virus coat protein attached to a synthetic polymeric carrier. The antiviral response was induced when the antigen was administered in complete Freund's adjuvant or when it was adm...

P2 is a fatty acid-binding protein expressed in vertebrate peripheral nerve myelin, where it may function in bilayer stacking and lipid transport. P2 binds to phospholipid membranes through its positively charged surface and a hydrophobic tip, and accommodates fatty acids inside its barrel structure. The structure of human P2 refined at the ultrahigh resolution of 0.93 Å allows detailed structu...

Focal adhesion kinase is an essential nonreceptor tyrosine kinase that plays an important role in development, in homeostasis and in the progression of human disease. Multiple stimuli activate FAK, which requires a change in structure from an autoinhibited to activated conformation. In the autoinhibited conformation the FERM domain associates with the catalytic domain of FAK and PI(4,5)P2 bindi...

The ribosome has a morphologically distinct structural feature called the stalk, recognized as a vital element for its function. The ribosomal P proteins constitute the main part of the eukaryotic ribosomal stalk, forming a pentameric structure P0-(P1-P2)(2). The group of P1/P2 proteins in eukaryotes is very diverse, and in spite of functional and structural similarities they do not fully compl...

Phosphatidylinositol 3,4-bisphosphate [PtdIns(3,4)P2] is a phosphoinositide that plays important roles in signal transduction, endocytosis, and cell migration among others. The intracellular distribution of PtdIns(3,4)P2 has mainly been studied by observing the distribution of GFP-tagged PtdIns(3,4)P2-binding protein domains in live cells and by labeling with anti-PtdIns(3,4)P2 antibody in fixe...

Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) signaling is transient and spatially confined in live cells. How this pattern of signaling regulates transmitter release and hormone secretion has not been addressed. We devised an optogenetic approach to control PI(4,5)P2 levels in time and space in insulin-secreting cells. Combining this approach with total internal reflection fluorescence mic...

We recently demonstrated that Pseudomonas aeruginosa PAO1 undergoes a pronounced phenotypic change when introduced into the intestines of rats during surgical injury. Recovered strains displayed a specific phenotype (termed the P2 phenotype) characterized by altered pyocyanin production, high collagenase activity, high swarming motility, low resistance to chloramphenicol, and increased killing ...

By high pressure liquid chromatography (HPLC) analysis, the occurrence of radiolabeled 3-phosphorylated phosphoinositides has been well documented in several cell systems, including agonist-stimulated platelets. The actual mass amounts and fatty acid composition of these unique lipids, however, have not been reported to date. In the present study, we report the mass and fatty acid composition o...

The phosphoinositide phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] regulates the activity of many actin-binding proteins and as such is an important modulator of cytoskeleton organization during cell migration, for example. In migrating cells actin remodeling is tightly regulated and localized; therefore, how the PI(4,5)P2 level is spatially and temporally regulated is crucial to understand...