The structure of the metal-nucleotide complex substrate for yeast hexokinase

A comparison has been made of the kinetic parameters obtained with yeast hexokinase using Mg²⁺ or Ni²⁺ as metal ion activator and ATP or tubercidin-5′-triphosphate as nucleotide substrate. It is concluded that the relative specificity of the enzyme for MgATP^2? does not involve a contribution arising from an interaction of the metal ion with the purine ring of the nucleotide.     

Changes in cerebral blood flow during a migraine attack.

Regional cerebral blood flow studies during a typical prodromal phase of a migraine attack in a young woman showed a global decrease of cerebral blood flow in the carotid artery territory. These studies were repeated during the subsequent headache phase of the same attack and hemispheric blood flow increased considerably. Ergotamine tartrate was then administered intramuscularly which brought definite relief of symptoms but no change in cerebral blood flow. Carotid angiography performed immediately afterwards showed retrograde filling of the proximal portion of the basilar artery, which suggested that the brain stem was the site of hyper-perfusion. These findings illustrate certain features underlying both the pathophysiology of migraine itself and its response to ergotamine preparations.     

Inhibition of cation cotransport by cholesterol enrichment of human red cell membranes.

1. Human red cells were enriched with cholesterol by incubation with lipid dispersions having a high cholesterol: phospholipid mol ratio and the kinetics of the furosemide-sensitive cotransport for Na+ and K+ were measured. 2. Influxes of both K+ and Na+ through this system were inhibited by 70 and 76% in cholesterol-rich cells (cholesterol: phospholipid mol ratio 1.80) and the Km of the furosemide-sensitive flux components for both K+ and Na+ decreased. 3. Effluxes of both K+ and Na+ are inhibited by furosemide and the magnitudes of these furosemide-sensitive components are markedly decreased in cholesterol-rich cells. 4. The inhibitory effect of cholesterol enrichment on this carrier-mediated transport of cations suggests that cholesterol may either alter the position of the carrier or retard its movement within a more viscous membrane micro-environment.     

The coreceptor CD2 uses plasma membrane microdomains to transduce signals in T cells

The interaction between a T cell and an antigen-presenting cell (APC) can trigger a signaling response that leads to T cell activation. Prior studies have shown that ligation of the T cell receptor (TCR) triggers a signaling cascade that proceeds through the coalescence of TCR and various signaling molecules (e.g., the kinase Lck and adaptor protein LAT [linker for T cell activation]) into microdomains on the plasma membrane. In this study, we investigated another ligand–receptor interaction (CD58–CD2) that facilities T cell activation using a model system consisting of Jurkat T cells interacting with a planar lipid bilayer that mimics an APC. We show that the binding of CD58 to CD2, in the absence of TCR activation, also induces signaling through the actin-dependent coalescence of signaling molecules (including TCR-ζ chain, Lck, and LAT) into microdomains. When simultaneously activated, TCR and CD2 initially colocalize in small microdomains but then partition into separate zones; this spatial segregation may enable the two receptors to enhance signaling synergistically. Our results show that two structurally distinct receptors both induce a rapid spatial reorganization of molecules in the plasma membrane, suggesting a model for how local increases in the concentration of signaling molecules can trigger T cell signaling.