Phosphatidylinositol Phosphate 5-Kinase Iγi2 in Association with Src Controls Anchorage-independent Growth of Tumor Cells

A fundamental property of tumor cells is to defy anoikis, cell death caused by a lack of cell-matrix interaction, and grow in an anchorage-independent manner. How tumor cells organize signaling molecules at the plasma membrane to sustain oncogenic signals in the absence of cell-matrix interactions remains poorly understood. Here, we describe a role for phosphatidylinositol 4-phosphate 5-kinase (PIPK) Iγi2 in controlling anchorage-independent growth of tumor cells in coordination with the proto-oncogene Src. PIPKIγi2 regulated Src activation downstream of growth factor receptors and integrins. PIPKIγi2 directly interacted with the C-terminal tail of Src and regulated its subcellular localization in concert with talin, a cytoskeletal protein targeted to focal adhesions. Co-expression of PIPKIγi2 and Src synergistically induced the anchorage-independent growth of nonmalignant cells. This study uncovers a novel mechanism where a phosphoinositide-synthesizing enzyme, PIPKIγi2, functions with the proto-oncogene Src, to regulate oncogenic signaling.     

Molecular Dynamics Simulation Studies of Zeolite-A. IV. Structure and Dynamics of NH4 + ions in a Rigid Dehydrated Zeolite-A

Abstract

In recent papers [1–3] we reported molecular dynamics simulation studies of ions and water molecules adsorbed in a rigid zeolite-A framework using a simple Lennard-Jones potential plus Coulomb potential with Ewald summation to investigate the structure and dynamics of the adsorbates. In the present paper the same technique is applied to study the local structure and dynamics of NH₄ ⁺ ions in a rigid dehydrated zeolite-A. During the preliminary equilibration, the unstable NH₄(4) type ion (the 12th ion) is pushed down to near a more stable 6-ring position in the α-cage that is already associated with an NH₄(1) type ion (the 1st) in the β-cage, which moves to another 6-ring position in the β-cage that is already associated with an NH₄(2) type ion (the 7th) in the α-cage. Calculated x, y, and z coordinates of some NH₄ ⁺ ions are in good agreement with those obtained from an X-ray diffraction experiment except that no NH₄(4) type ion is found and there are six NH₄(2) type ions instead of 0.5 and 5.5 occupancy. The analyses of calculated interatomic distances and time correlation functions of these ions indicate that the NH₄(1 – 1) and NH₄(3) type ions are associated loosely with only one O (3) atom of the 6-ring and with only one O (1) atom of the 8-ring windows, respectively, while the NH₄(1–2) and NH₄(2) type ions are associated strongly with two or three O (3) atoms of the 6-ring windows in the α- and β-cages, respectively. The analysis of hydrogen bond time correlation functions of these ions indicate that about one, two or three, three, and one hydrogen bond of each NH₄(1–1), NH₄(1–2), NH₄(2) and NH₄(3) type ion is kept for 1.4, 21, 75, and 1.4 ps, respectively, before breakup of the hydrogen bond occurs and significant exchange of O atom hydrogen-bonded to the ion.     

Cryptic speciation in the field vole: a multilocus approach confirms three highly divergent lineages in Eurasia

Species are generally described from morphological features, but there is growing recognition of sister forms that show substantial genetic differentiation without obvious morphological variation and may therefore be considered ‘cryptic species’. Here, we investigate the field vole (Microtus agrestis), a Eurasian mammal with little apparent morphological differentiation but which, on the basis of previous sex‐linked nuclear and mitochondrial DNA (mtDNA) analyses, is subdivided into a Northern and a Southern lineage, sufficiently divergent that they may represent two cryptic species. These earlier studies also provided limited evidence for two major mtDNA lineages within Iberia. In our present study, we extend these findings through a multilocus approach. We sampled 163 individuals from 46 localities, mainly in Iberia, and sequenced seven loci, maternally, paternally and biparentally inherited. Our results show that the mtDNA lineage identified in Portugal is indeed a distinct third lineage on the basis of other markers as well. In fact, multilocus coalescent‐based methods clearly support three separate evolutionary units that may represent cryptic species: Northern, Southern and Portuguese. Divergence among these units was inferred to have occurred during the last glacial period; the Portuguese lineage split occurred first (estimated at c. 70 000 bp ), and the Northern and Southern lineages separated at around the last glacial maximum (estimated at c. 18 500 bp ). Such recent formation of evolutionary units that might be considered species has repercussions in terms of understanding evolutionary processes and the diversity of small mammals in a European context.