Mutations of Ros differentially effecting signal transduction pathways leading to cell growth versus transformation.

The Journal of Biological Chemistry
C S ZongL H Wang

Abstract

The signaling functions of the oncogenic protein-tyrosine kinase v-Ros were studied by systematically mutating the tyrosine residues in its cytoplasmic domain. The carboxyl mutation of Tyr-564 produces the most pronounced inhibitory effect on v-Ros autophosphorylation and interaction with phospholipase Cgamma. A cluster of 3 tyrosine residues, Tyr-414, Tyr-418, and Tyr-419, within the PTK domain of v-Ros plays an important role in modulating its kinase activity. The mutant F419 and the mutant DI, deleting 6-amino acids near the catalytic loop, retain wild type protein tyrosine kinase and mitogenic activities, but have dramatically reduced oncogenicity. Both mutant proteins are able to phosphorylate or activate components in the Ras/microtubule-associated protein kinase signaling pathway. However, F419 mutant protein is unable to phosphorylate insulin receptor substrate 1 (IRS-1) or promote association of IRS-1 with phosphatidylinositol 3-kinase. This tyrosine residue in the context of the NDYY motif may define a novel recognition site for IRS-1. Both F419 and DI mutants display impaired ability to induce tyrosine phosphorylation of a series of cytoskeletal and cell-cell interacting proteins. Thus the F419 and DI mutations defin...Continue Reading

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Citations

Jun 4, 1999·Progress in Biophysics and Molecular Biology·S R Hubbard
Sep 5, 2001·Molecular and Cellular Biology·R HrdlickováH R Bose
Sep 10, 2008·Biochimica Et Biophysica Acta·Jaime AcquavivaAl Charest
Feb 6, 2007·Atherosclerosis·Mitsutoshi OguriYoshiji Yamada
Aug 6, 2010·Medicinal Research Reviews·Ibrahim Mustafa El-DeebSo Ha Lee
Sep 22, 2005·American Journal of Human Genetics·Dov ShiffmanJohn P Kane
Jun 4, 2016·Future Oncology·Arnaud Uguen, Marc De Braekeleer
Oct 4, 2016·Journal of Molecular Graphics & Modelling·Disha PathakOm Silakari
Jun 21, 2008·Stroke; a Journal of Cerebral Circulation·Yoshiji YamadaYoshinori Nozawa
Apr 17, 2012·Expert Review of Anticancer Therapy·Sai-Hong Ignatius OuRoss A Soo
Jan 19, 2002·The Journal of Biological Chemistry·Kevin T NguyenLu-Hai Wang

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