Marignani, Paola
Permanent URI for this collectionhttps://hdl.handle.net/10222/44342
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Item Open Access Loss of lkb1 Expression Reduces the Latency of ErbB2-Mediated Mammary Gland Tumorigenesis, Promoting Changes in Metabolic Pathways(2013-02) Andrade-Vieira, Rafaela; Xu, Zhaolin; Colp, Patricia; Marignani, Paola A.No abstract available.Item Open Access Item Open Access Multiple phosphoinositide 3-kinase-dependent steps in activation of protein kinase B(2002-09) Scheid, M. P.; Marignani, P. A.; Woodgett, J. R.The protein kinase B (PKB)/Akt family of serine kinases is rapidly activated following agonist-induced stimulation of phosphoinositide 3-kinase (PI3K). To probe the molecular events important for the activation process, we employed two distinct models of posttranslational inducible activation and membrane recruitment. PKB induction requires phosphorylation of two critical residues, threonine 308 in the activation loop and serine 473 near the carboxyl terminus. Membrane localization of PKB was found to be a primary determinant of serine 473 phosphorylation. PI3K activity was equally important for promoting phosphorylation of serine 473, but this was separable from membrane localization. PDK1 phosphorylation of threonine 308 was primarily dependent upon prior serine 473 phosphorylation and, to a lesser extent, localization to the plasma membrane. Mutation of serine 473 to alanine or aspartic acid modulated the degree of threonine 308 phosphorylation in both models, while a point mutation in the substrate-binding region of PDK1 (L155E) rendered PDK1 incapable of phosphorylating PKB. Together, these results suggest a mechanism in which 3' phosphoinositide lipid-dependent translocation of PKB to the plasma membrane promotes serine 473 phosphorylation, which is, in turn, necessary for PDK1-mediated phosphorylation of threonine 308 and, consequentially, full PKB activation.Item Open Access Correction: Loss of Expression Reduces the Latency of ErbB2-Mediated Mammary Gland Tumorigenesis, Promoting Changes in Metabolic Pathways(2013-02) Andrade-Vieira, R.; Xu, Z.; Colp, P.; Marignani, P. A.[This corrects the article on p. e56567 in vol. 8.].Item Open Access LKB1 Catalytic Activity Contributes to Estrogen Receptor alpha Signaling(2009-06) Nath-Sain, Suchita; Marignani, Paola A.No abstract available.