Effects of H-Ras Disease Mutations on Binding to the Ras Binding Domain of PI3Ky Measured by Micro-Scale Thermophoresis

H-Ras is a G-protein responsible for the activation of multiple signaling pathways that control cell growth. Our primary interest is examining its role in the regulation of the phosphoinositide-3-kinase (PI3K) signaling cascade, as H-Ras has been previously shown to recruit PI3K to the plasma membrane where this lipid kinase phosphorylates PIP2 to PIP3, a signal for cellular growth. The H-Ras-PI3K-PIP3 signaling pathway is known to be highly oncogenic, with constitutive activation of H-Ras leading to increased PIP3 production and cell growth. We hypothesize that disease-linked mutations on the binding interface between Ras and PI3K increase the affinity for complex formation, thereby recruiting more PI3K to the membrane and increasing PIP3 production. The affinity of five H-Ras mutants for the PI3Ky Ras binding domain (PI3Ky-RBD) were measured using Micro-Scale Thermophoresis (MST). The findings reveal that the H-Ras Y64H and E63K mutations trigger significant increases in the affinity of H-Ras binding to PI3Ky-RBD. Unexpectedly, the common cancer-linked mutation H-Ras G12S may also increase the affinity of the H-Ras-PI3Ky-RBD complex, potentially adding a second mechanism to the current model of G12S-triggered oncogenesis. Two control mutations (D38E and Y40C) are observed to significantly weaken H-Ras binding to PI3Ky-RBD as predicted. Collectively our results support the existence of a novel disease mechanism by which disease-linked Ras mutations stimulate PI3K and PIP3 signaling by increasing the affinity of Ras binding to PI3K, in turn recruiting additional PI3K to the membrane and triggering increased PIP3 production and the associated unregulated cell growth.</p

<Ioustinou tou philosophou kai parturos Epistolê pros Diogneton, kai logos pros Hellênas>. Justini Philosophi et martyris Epistola ad Diognetum, et Oratio ad Graecos, nunc primum luce et latinitate donatae ab Henrico Stephano. Ejusdem Henr. Stephani annotationibus additum est Jo. Jacobi Beureri de quorundam locorum partim interpretatione partim emendatione judicium. Tatiani, discipuli Justini, quaedam

GLN-3550Adams, Cambridge, D 493CDM, p. 134Kecskeméti, Estienne, n° 16

Corpus apologetarum christianorum saeculi secundi /

Greek and Latin on opposite pages.Each volume has also special title-page.Includes bibliographical references.Volumen I-V. Iustinus Philosophus et Martyr: Iustini Philosophi et Martyris Opera quae feruntur omnia. Ad optimos libros Mss. nunc primum aut denuo collatos recensuit prolegomenis et commentariis instruxit translatione latina ornavit indices adiecit / Io. Car. Th. eqves de Otto. Tomi I, Pars I-II. Opera Iustini indubitata. Editio tertia, plurimum aucta et emendata. Accedunt specimina lithogr. duorum codicum mss. 1876-1877. Tomus II. Opera Iustini addubitata. Fragmenta Operum Iustini deperditorum. Acta Martyrii Iustini et sociorum. Editio tertia, plurimum aucta et emendata. Accedunt specimina lithogr. trium codicum mss. 1879. Tomi III. Pars I. Opera Iustini subditicia. Fragmenta Pseudo-Iustini. Editio tertia, plurimum aucta et emendata. Accedunt specimina lithogr. duorum codicum mss. 1880. Pars II. Opera Iustini subditicia.Fragmenta Pseudo-Iustini. Editio tertia, plurimum aucta et emendata. 1881.Mode of access: Internet

Believing in God the Father: Interpreting a phrase from the Apostle’s Creed

Prof. Dr Sarot is participating in the research project, ‘Biblical Theology and Hermeneutics’, directed by Prof. Dr Andries G. van Aarde, Post Retirement Professor, Department of New Testament Studies, Faculty of Theology, University of PretoriaIn our days, the creedal phrase ‘I believe in God the Father almighty’ is interpreted primarily along Trinitarian lines: It is applied to God as the Father of Jesus Christ. Here I argue that it has a dual background: in Jesus’ prayer practice, in which He consistently addressed God as ‘Father’, and in the Hellenistic habit of referring to the Creator as ‘Father’. I discuss Jesus’ use of the term ‘Father’ against its Old Testament background, and argue that it primarily points to the intimacy of Jesus’ relationship with His father. Against the Hellenistic background, however, the metaphor ‘Father’ means ‘he who brings forth effortlessly’. Finally, I discuss some gender issues connected with the use of the term ‘Father’ for God.http://www.hts.org.zaam2016New Testament Studie