Erythroid Cells Rendered Erythropoietin Independent by Infection with Friend Spleen Focus-Forming Virus Show Constitutive Activation of Phosphatidylinositol 3-Kinase and Akt Kinase: Involvement of Insulin Receptor Substrate-Related Adapter Proteins

• DOI: 10.1128/jvi.74.7.3037-3045.2000
• Publication Date: 2002-07-27T10:06:37Z
• Authors: Kazuo Nishigaki; Charlotte Hanson; Takashi Ohashi; Delores Thompson; Karen Muszynski; Sandra Ruscetti
• Keywords: Erythropoietin receptor; Cyclin-dependent kinase 9

ABSTRACT The erythroleukemia-inducing Friend spleen focus-forming virus (SFFV) encodes a unique envelope glycoprotein which allows erythroid cells to proliferate and differentiate in the absence of erythropoietin (Epo). In an effort understand how SFFV causes Epo independence, we have been examining rendered factor independent by infection for constitutive activation signal-transducing molecules. Previous studies from our laboratory showed that various molecules known be activated Epo, including Stat proteins components Raf-1/MAP kinase pathway, are constitutively SFFV-infected Epo. Since another signal transduction pathway involving phosphatidylinositol 3-kinase (PI 3-kinase) after stimulation plays important role cell proliferation differentiation, carried out determine if this was also Our show PI is with activity, but not receptor tyrosine phosphorylation, required these We further grown associates insulin substrate (IRS)-related adapter IRS-2, Gab1, Gab2, phosphorylated cells. Finally, Akt, protein one downstream effectors 3-kinase, SHIP, lipid phosphatase Akt through both results indicate induction independence requires suggest may occur primarily interaction IRS-related