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154 Newest Publications of Portland Press

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Phosphorylation of the guanine-nucleotide-exchange factor CalDAG-GEFI by protein kinase A regulates Ca2+-dependent activation of platelet Rap1b GTPase

01-07-2013 | Guidetti GF; Manganaro D; Consonni A; Canobbio I; Balduini C; Torti M, Biochemical Journal, 2013

In blood platelets the small GTPase Rap1b is activated by cytosolic Ca2+ and promotes integrin αIIbβ3 inside-out activation and platelet aggregation. cAMP is the major inhibitor of platelet function and antagonizes Rap1b stimulation through a mechanism that remains unclear. In the present ...

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Elevated SGK1 predicts resistance of breast cancer cells to Akt inhibitors

15-06-2013 | Sommer EM; Dry H; Cross D; Guichard S; Davies BR; Alessi DR, Biochemical Journal, 2013

The majority of human cancers harbour mutations promoting activation of the Akt protein kinase, and Akt inhibitors are being evaluated in clinical trials. An important question concerns the understanding of the innate mechanisms that confer resistance of tumour cells to Akt inhibitors. SGK ...

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Structure-guided optimization of protein kinase inhibitors reverses aminoglycoside antibiotic resistance

12-06-2013 | Stogios P; Spanogiannopoulos P; Evdokimova E; Egorova O; Shakya T; Todorovic N; Capretta A; Wright G; Savchenko A, Biochemical Journal, 2013

Activity of the aminoglycoside phosphotransferase APH(3’)-Ia leads to resistance to aminoglycoside antibiotics in pathogenic Gram-negative bacteria, and contributes to the clinical obsolescence of this class of antibiotics. One strategy to rescuing compromised antibiotics such as ...

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Crystal structures of S6K1 provide insights into the regulation mechanism of S6K1 by the hydrophobic motif

03-06-2013 | Wang J; Zhong C; Wang F; Qu F; Ding J, Biochemical Journal, 2013

The activity of the ribosome protein subunit 6 kinase 1 (S6K1) is stimulated by phosphorylation of Thr389 in the hydrophobic motif by mTORC1 and phosphorylation of Thr229 in the activation loop by PDK1; however, the order of the two events is still ambiguous. Here we report six crystal ...

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Spermidine promotes adipogenesis of 3T3-L1 cells by preventing interaction of ANP32 with HUR and PP2A

14-05-2013 | Hyv{o}nen M; Koponen T; Weisell J; Pietil{a} M; Khomutov A; Veps{a}l{a}inen J; Alhonen L; Kein{a}nen T, Biochemical Journal, 2013

We previously showed that the polyamine spermidine is indispensable for differentiation of 3T3-L1 preadipocytes. Here, we studied the mechanism of spermidine function by using polyamine biosynthesis inhibitor α-difluoromethylornithine in combination with the metabolically stable polyamine ...

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skNAC depletion stimulates myoblast migration and perturbs sarcomerogenesis by enhancing calpain 1 and 3 activity

13-05-2013 | Berkholz J; Zakrzewicz A; Munz B, Biochemical Journal, 2013

Skeletal and heart muscle specific variant of nascent polypeptide associated complex (skNAC) is a skeletal and heart muscle-specific protein known to be involved in the regulation of sarcomerogenesis. The respective mechanism, however, is largely unknown. Here, we demonstrate that skNAC ...

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Phosphorylation of the guanine-nucleotide exchange factor CalDAG-GEFI by protein kinase A regulates Ca{Less than}sup{Greater than}2{+}{Less than}/sup{Greater than}-dependent activation of platelet Rap1b GTPase

19-04-2013 | Guidetti G; Manganaro D; Consonni A; Canobbio I; Balduini C; Torti M, Biochemical Journal, 2013

In blood platelets, the small GTPase Rap1b is activated by cytosolic Ca2+, and promotes integrin aIIbb3 inside-out activation and platelet aggregation. cAMP is the major inhibitor of platelet function and antagonizes Rap1b stimulation through a mechanism that remains unclear. In this work we ...

more

Elevated SGK1 predicts resistance of breast cancer cells to Akt inhibitors

15-04-2013 | Sommer E; Dry H; Cross D; Guichard S; Davies B; Alessi D, Biochemical Journal, 2013

The majority of human cancers harbour mutations promoting activation of the Akt protein kinase and Akt inhibitors are being evaluated in clinical trials. An important question concerns understanding the innate mechanisms that confer resistance of tumour cells to Akt inhibitors. The Serum ...

more

HER2 stabilizes survivin while concomitantly down-regulating survivin gene transcription by suppressing Notch cleavage

01-04-2013 | Ju J-h; Yang W; Oh S; Nam K; Lee K-m; Noh D-y; Shin I, Biochemical Journal, 2013

In breast cancer, the HER2 (human epidermal growth factor receptor 2) receptor tyrosine kinase is associated with extremely poor prognosis and survival. Notch signalling has a key role in cell-fate decisions, especially in cancer-initiating cells. The Notch intracellular domain produced by ...

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Mechanistic studies of FosB: a divalent-metal-dependent bacillithiol-S-transferase that mediates fosfomycin resistance in Staphylococcus aureus

01-04-2013 | Roberts AA; Sharma SV; Strankman AW; Duran SR; Rawat M; Hamilton CJ, Biochemical Journal, 2013

FosB is a divalent-metal-dependent thiol-S-transferase implicated in fosfomycin resistance among many pathogenic Gram-positive bacteria. In the present paper, we describe detailed kinetic studies of FosB from Staphylococcus aureus (SaFosB) that confirm that bacillithiol (BSH) is its ...

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