Abstract-Modulation 6 -8 This mechanism seems to underlie the increased vascular spontaneous tone observed in hypertensive rats. 9 However, how PI3K is able to regulate Ca 2ϩ channels activity remains to be elucidated. 10 Class I PI3Ks are enzymes that selectively phosphorylate the 3Ј-OH position of the PI(4,5)P 2 inositol ring in vivo to generate PI(3,4,5)P 3 , further metabolized by inositol lipid phosphatases to PI(3,4)P 2 . PI(3,4)P 2 and PI(3,4,5)P 3 are absent in resting cells, increase on class I PI3K activation during cellular stimulation, and interact with pleckstrin homology (PH) domains of cellular proteins to transduce signal. Class I PI3Ks have been subclassified according to their structure and mode of activation by cell surface receptors. Class IA PI3Ks are heterodimers composed of a catalytic subunit (the ubiquitous p110␣ or more tissue-restricted p110␤, or p110␦) tightly complexed to a regulatory adapter subunit (p85␣, p85␤, p55, or their splice variants). These regulatory subunits dock the holoenzyme to the membrane through interactions with specific phosphotyrosyl-containing sequences within receptor tyrosine kinases or other membrane-associated proteins. Class IB PI3K is composed of the p110␥ catalytic subunit associated with a p101 regulatory protein. PI3K␥ is specifically stimulated by G␤␥ dimers liberated on G protein-coupled receptor (GPCR) activation. The p110␥ catalytic subunit contains all the structural elements necessary for G␤␥-induced stimulation. The p101 noncatalytic regulatory subunit, which is able to bind lipid substrates, increase p110␥ activity. 11 PI3K␤ is synergistically activated by GPCRs and receptor tyrosine kinases. Like for other class IA enzymes, phosphotyrosyl peptide interaction with the p85 regulatory subunit leads to activation of PI3K␤. However, p110␤ catalytic subunits can be directly activated by membrane-bound ␤␥ dimers. 12 Original

ATP-mediated Ca2+ signalling was studied in freshly isolated rat portal vein myocytes by means of a laser confocal microscope and the patch-clamp technique.2. In vascular myocytes held at _60 mV, ATP induced a large inward current that was supported mainly by activation of P2X1 receptors, although other P2X receptor subtypes (P2X3, P2X4 and P2X5) were revealed by reverse transcription-polymerase chain reaction.

In order to better understand the mechanisms of actinide uptake by specific biomolecules, it is essential to explore the intramolecular interactions between the cation and the protein binding site. Although this has long been done for widely investigated transition metals, very few studies have been devoted to complexation mechanisms of actinides by active chelation sites of metalloproteins. In this field, X-ray absorption spectroscopy has been extensively used as a structural and electronic metal cation probe. The two examples that are presented here are related to two metalloproteins in charge of iron transport and storage in eukaryote cells: transferrin and ferritin. U(VI)O 2 2+ , Np(IV) and Pu(IV) have been selected because of their possible role as contaminant from the geosphere.

No abstract