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Articles

The mTORC2 signaling network: targets and cross-talks

In Collection

Cell signaling in the 21st century

Aparna Ragupathi, Christian Kim, Estela Jacinto

Biochem J (2024) 481 (2): 45–91.

https://doi.org/10.1042/BCJ20220325

Published: 25 January 2024

... to allow metabolic reprogramming and ensure cell survival remains poorly understood. A variety of downstream effectors of mTORC2 have been identified but the most well-characterized mTORC2 substrates include Akt, PKC, and SGK, which are members of the AGC protein kinase family. Here, we review how mTORC2...

View articletitled, The mTORC2 signaling network: targets and cross-talks

Articles

Activity of EGFR transmembrane region variants indicates specific transmembrane dimers are not required for EGFR activity

Foteini Bartzoka, Monica Gonzalez-Magaldi, Patrick O. Byrne, Nicole I. Callery, Kalina Hristova, Daniel J. Leahy

Biochem J (2022) 479 (24): 2465–2475.

https://doi.org/10.1042/BCJ20220472

Published: 19 December 2022

... and stimulate phosphorylation of downstream effectors Erk and Akt. Our results indicate that many transmembrane sequences, including polyleucine, are compatible with EGFR activity and provide no evidence for specific transmembrane dimers regulating EGFR function. Wild-type EGFR and each of the EGFR TM...

View articletitled, Activity of EGFR transmembrane region variants indicates specific transmembrane dimers are not required for EGFR activity

Includes: Supplementary data

Articles

Phosphoproteomics reveals that the hVPS34 regulated SGK3 kinase specifically phosphorylates endosomal proteins including Syntaxin-7, Syntaxin-12, RFIP4 and WDR44

Nazma Malik, Raja S. Nirujogi, Julien Peltier, Thomas Macartney, Melanie Wightman, Alan R. Prescott, Robert Gourlay, Matthias Trost, Dario R. Alessi, Athanasios Karapetsas

Biochem J (2019) 476 (20): 3081–3107.

https://doi.org/10.1042/BCJ20190608

Published: 30 October 2019

... pathway. SGKs are homologous to Akt and these kinases display overlapping specificity and phosphorylate several substrates at the same residues, such as TSC2 to promote tumor growth by switching on the mTORC1 pathway. The SGK3 isoform is up-regulated in breast cancer cells treated with PI3K or Akt...

View articletitled, Phosphoproteomics reveals that the hVPS34 regulated SGK3 kinase specifically phosphorylates endosomal proteins including Syntaxin-7, Syntaxin-12, RFIP4 and WDR44

Includes: Supplementary data

Articles

Loss of GCN5L1 in cardiac cells disrupts glucose metabolism and promotes cell death via reduced Akt/mTORC2 signaling

Janet R. Manning, Dharendra Thapa, Manling Zhang, Michael W. Stoner, Javier Traba, Catherine Corey, Sruti Shiva, Michael N. Sack, Iain Scott

Biochem J (2019) 476 (12): 1713–1724.

https://doi.org/10.1042/BCJ20190302

Published: 19 June 2019

.... In this study, we sought to determine the mechanism by which GCN5L1 impacts energy substrate utilization and mitochondrial health. We find that hypoxia and reoxygenation (H/R) leads to a reduction in cell viability and Akt phosphorylation in GCN5L1 knockdown AC16 cardiomyocytes, in parallel with elevated...

View articletitled, Loss of GCN5L1 in cardiac cells disrupts glucose metabolism and promotes cell death via reduced Akt/mTORC2 signaling

Includes: Supplementary data

Articles

The pro-inflammatory cytokines IFNγ/TNFα increase chromogranin A-positive neuroendocrine cells in the colonic epithelium

José Antonio Hernández-Trejo, Dimelza Suárez-Pérez, Itzel Zenidel Gutiérrez-Martínez, Omar Eduardo Fernandez-Vargas, Carolina Serrano, Aurora Antonia Candelario-Martínez, Marco Antonio Meraz-Ríos, Alí Francisco Citalán-Madrid, Marcela Hernández-Ruíz, Elba Reyes-Maldonado, Ricardo Valle-Rios, Jacobo H. Feintuch-Unger, Michael Schnoor, Nicolás Villegas-Sepúlveda, Oscar Medina-Contreras, Porfirio Nava

Biochem J (2016) 473 (21): 3805–3818.

https://doi.org/10.1042/BCJ20160390

Published: 27 October 2016

... A (CgA) in the colonic mucosa of C57BL/6J mice. CgA-positive cells were non-proliferating cells enriched with inactive phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and autophagy markers. Moreover, inhibition of Akt and autophagy prevented the increase in CgA-positive cells after IFNγ...

View articletitled, The pro-inflammatory cytokines IFNγ/TNFα increase chromogranin A-positive neuroendocrine cells in the colonic epithelium

Includes: Supplementary data

Articles

Insulin signalling and glucose transport in the ovary and ovarian function during the ovarian cycle

In Collection

Celebrating 100 years of insulin research

Joëlle Dupont, Rex J. Scaramuzzi

Biochem J (2016) 473 (11): 1483–1501.

https://doi.org/10.1042/BCJ20160124

Published: 27 May 2016

...), PI3K (phosphoinositide kinase)/Akt and MAPK (mitogen-activated protein kinase). Most of these insulin pathways are probably also active in the ovary and their ability to interact with each other and also with follicle-stimulating hormone (FSH) and luteinizing hormone (LH) signalling pathways enables...

View articletitled, Insulin signalling and glucose transport in the ovary and ovarian function during the ovarian cycle

Articles

Gambogic acid inhibits osteoclast formation and ovariectomy-induced osteoporosis by suppressing the JNK, p38 and Akt signalling pathways

Jianjun Ma, Yan Ma, Xuqiang Liu, Shuai Chen, Chao Liu, An Qin, Shunwu Fan

Biochem J (2015) 469 (3): 399–408.

https://doi.org/10.1042/BJ20150151

Published: 23 July 2015

... that GBA prevented ovariectomy-induced bone loss in a dose-dependent manner. Moreover, we demonstrated that GBA suppressed RANKL (receptor activator of nuclear factor κB ligand)-induced JNK (c-Jun N-terminal kinase), p38 and Akt phosphorylation. Taken together, our results demonstrate that GBA inhibits...

View articletitled, Gambogic acid inhibits osteoclast formation and ovariectomy-induced osteoporosis by suppressing the JNK, p38 and Akt signalling pathways

Articles

Akt/PKB: one kinase, many modifications

Guillermo Risso, Matías Blaustein, Berta Pozzi, Pablo Mammi, Anabella Srebrow

Biochem J (2015) 468 (2): 203–214.

https://doi.org/10.1042/BJ20150041

Published: 22 May 2015

...Guillermo Risso; Matías Blaustein; Berta Pozzi; Pablo Mammi; Anabella Srebrow Akt/PKB, a serine/threonine kinase member of the AGC family of proteins, is involved in the regulation of a plethora of cellular processes triggered by a wide diversity of extracellular signals and is thus considered...

View articletitled, Akt/PKB: one kinase, many modifications

Articles

Lyn kinase plays important roles in erythroid expansion, maturation and erythropoietin receptor signalling by regulating inhibitory signalling pathways that control survival

Neli S. Slavova-Azmanova, Nicole Kucera, Alison Louw, Jiulia Satiaputra, Adley Handoko, Peter Singer, Leah Stone, David J. McCarthy, S. Peter Klinken, Margaret L. Hibbs, Evan Ingley

Biochem J (2014) 459 (3): 455–466.

https://doi.org/10.1042/BJ20130903

Published: 11 April 2014

..., and late stage Lyn −/− erythroblasts were retarded in completing morphological maturation ex vivo . Furthermore, immortalized Lyn −/− erythroblasts were slower growing, less viable and inhibited in their differentiation. Signalling studies showed that Lyn was required for both positive GAB2/Akt/FoxO3...

View articletitled, Lyn kinase plays important roles in erythroid expansion, maturation and erythropoietin receptor signalling by regulating inhibitory signalling pathways that control survival

Includes: Supplementary data

Articles

Phosphorylation by Akt within the ST loop of AMPK-α1 down-regulates its activation in tumour cells

Simon A. Hawley, Fiona A. Ross, Graeme J. Gowans, Priyanka Tibarewal, Nicholas R. Leslie, D. Grahame Hardie

Biochem J (2014) 459 (2): 275–287.

https://doi.org/10.1042/BJ20131344

Published: 28 March 2014

...Simon A. Hawley; Fiona A. Ross; Graeme J. Gowans; Priyanka Tibarewal; Nicholas R. Leslie; D. Grahame Hardie The insulin/IGF-1 (insulin-like growth factor 1)-activated protein kinase Akt (also known as protein kinase B) phosphorylates Ser 487 in the ‘ST loop’ (serine/threonine-rich loop) within...

View articletitled, Phosphorylation by Akt within the ST loop of AMPK-α1 down-regulates its activation in tumour cells

Includes: Supplementary data

Articles

Insulin-stimulated leptin secretion requires calcium and PI3K/Akt activation

Yue Wang, Yusuf Ali, Chun-Yan Lim, Wanjin Hong, Zhiping P. Pang, Weiping Han

Biochem J (2014) 458 (3): 491–498.

https://doi.org/10.1042/BJ20131176

Published: 28 February 2014

...-regulating leptin synthesis and that leptin-containing vesicles go through the ER–Golgi route. The PI3K (phosphoinositide 3-kinase)/Akt, but not MAPK (mitogen-activated protein kinase), pathway is involved in ISLS in vitro and in vivo . Although Ca 2+ triggers synaptic vesicle and secretory granule...

View articletitled, Insulin-stimulated leptin secretion requires calcium and PI3K/Akt activation

Includes: Supplementary data

Articles

AKT-ing out: SGK kinases come to the fore

Larissa S. Moniz, Bart Vanhaesebroeck

Biochem J (2013) 452 (3): e11–e13.

https://doi.org/10.1042/BJ20130617

Published: 31 May 2013

... that pre-exist as parallel signalling pathways. This aspect is explored by the Alessi group and collaborators from AstraZeneca in this issue of the Biochemical Journal , who identify a subset of breast cancer cell lines that are intrinsically resistant to Akt inhibition through constitutive up-regulation...

View articletitled, AKT-ing out: SGK kinases come to the fore

Articles

A requirement for wild-type Ras isoforms in mutant KRas-driven signalling and transformation

Carolyn Bentley, Stefanie S. Jurinka, Noelyn M. Kljavin, Steffan Vartanian, Sree R. Ramani, Lino C. Gonzalez, Kebing Yu, Zora Modrusan, Pan Du, Richard Bourgon, Richard M. Neve, David Stokoe

Biochem J (2013) 452 (2): 313–320.

https://doi.org/10.1042/BJ20121578

Published: 10 May 2013

... of either WT isoform of Ras compromised growth-factor-dependent signalling through the ERK (extracellular-signal-regulated kinase) pathway. In addition, the disruption of HRas hindered the activation of Akt and subsequent downstream signalling. This was associated with decreased proliferation, increased...

View articletitled, A requirement for wild-type Ras isoforms in mutant KRas-driven signalling and transformation

Includes: Supplementary data

Articles

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

Ji-hyun Ju, Wonseok Yang, Sunhwa Oh, KeeSoo Nam, Kyung-min Lee, Dong-young Noh, Incheol Shin

Biochem J (2013) 451 (1): 123–134.

https://doi.org/10.1042/BJ20121716

Published: 14 March 2013

... complex to ubiquitinate survivin. In addition, Thr 34 of survivin was shown to be the most important residue in determining survivin stability upon phosphorylation after HER2/Akt/CDK1 (cyclin-dependent kinase 1)–cyclin B1 signalling. The results of the present study show the combinatorial effects of HER2...

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

Includes: Supplementary data

Articles

Akt is efficiently activated by PIF-pocket- and PtdIns(3,4,5) P 3 -dependent mechanisms leading to resistance to PDK1 inhibitors

Ayaz Najafov, Natalia Shpiro, Dario R. Alessi

Biochem J (2012) 448 (2): 285–295.

https://doi.org/10.1042/BJ20121287

Published: 07 November 2012

...Ayaz Najafov; Natalia Shpiro; Dario R. Alessi Mutations leading to inappropriate activation of Akt isoforms contribute to proliferation and survival of a significant proportion of human cancers. Akt is activated by phosphorylation of its T-loop residue (Thr 308 ) by PDK1 (3-phosphoinositide...

View articletitled, Akt is efficiently activated by PIF-pocket- and PtdIns(3,4,5) P 3 -dependent mechanisms leading to resistance to PDK1 inhibitors

Includes: Supplementary data

Articles

ALAS1 gene expression is down-regulated by Akt-mediated phosphorylation and nuclear exclusion of FOXO1 by vanadate in diabetic mice

Leda M. Oliveri, Carlos Davio, Alcira M. del C. Batlle, Esther N. Gerez

Biochem J (2012) 442 (2): 303–310.

https://doi.org/10.1042/BJ20111005

Published: 13 February 2012

... for the treatment of acute porphyria attacks. Both ALAS1 mRNA and protein content were induced in diabetic animals, accompanied by decreased Akt phosphorylation and increased nuclear FOXO1, PGC-1α and FOXO1–PGC-1α complex levels. Vanadate reversed ALAS1 induction, with a concomitant PI3K (phosphoinositide 3-kinase...

View articletitled, ALAS1 gene expression is down-regulated by Akt-mediated phosphorylation and nuclear exclusion of FOXO1 by vanadate in diabetic mice

Articles

S6K inhibition renders cardiac protection against myocardial infarction through PDK1 phosphorylation of Akt

Ruomin Di, Xiangqi Wu, Zai Chang, Xia Zhao, Qiuting Feng, Shuangshuang Lu, Qing Luan, Brian A. Hemmings, Xinli Li, Zhongzhou Yang

Biochem J (2012) 441 (1): 199–207.

https://doi.org/10.1042/BJ20110033

Published: 14 December 2011

...-treated controls. Consistently, inhibition of S6K with PF-4708671 displayed similar protection against MI as rapamycin. Mechanistically, we observed significantly enhanced Thr 308 phosphorylation and activation of Akt in rapamycin- and PF-4708671-treated hearts. Cardiomyocyte-specific deletion of PDK1...

View articletitled, S6K inhibition renders cardiac protection against myocardial infarction through PDK1 phosphorylation of Akt

Includes: Supplementary data

Articles

Suppression of TG-interacting factor sensitizes arsenic trioxide-induced apoptosis in human hepatocellular carcinoma cells

Zi-Miao Liu, Joseph T. Tseng, Duang-Yang Hong, Huei-Sheng Huang

Biochem J (2011) 438 (2): 349–358.

https://doi.org/10.1042/BJ20101653

Published: 12 August 2011

... the interaction between HuR and TGIF mRNA, and reduction of HuR expression inhibited ATO-induced TGIF expression. Moreover, the EGFR (epidermal growth factor receptor)/PI3K (phosphoinositide 3-kinase)/Akt pathway was shown to mediate the post-transcriptional regulation of TGIF in response to ATO. Finally, we also...

View articletitled, Suppression of TG-interacting factor sensitizes arsenic trioxide-induced apoptosis in human hepatocellular carcinoma cells

Articles

ER stress modulates cellular metabolism

Xiaoli Wang, Colins O. Eno, Brian J. Altman, Yanglong Zhu, Guoping Zhao, Kristen E. Olberding, Jeffrey C. Rathmell, Chi Li

Biochem J (2011) 435 (1): 285–296.

https://doi.org/10.1042/BJ20101864

Published: 15 March 2011

... processes may be related to a reduction in cell-surface GLUT1 (glucose transporter 1) levels which, in turn, may reflect decreased Akt signalling. These results suggest that ER stress exerts profound effects on several central metabolic processes which may help to explain cell death arising from ER stress...

View articletitled, ER stress modulates cellular metabolism

Includes: Supplementary data

Articles

Contraction regulates site-specific phosphorylation of TBC1D1 in skeletal muscle

Kanokwan Vichaiwong, Suneet Purohit, Ding An, Taro Toyoda, Niels Jessen, Michael F. Hirshman, Laurie J. Goodyear

Biochem J (2010) 431 (2): 311–320.

https://doi.org/10.1042/BJ20101100

Published: 28 September 2010

... and function. We studied TBC1D1 phosphorylation on three predicted AMPK (AMP-activated protein kinase) phosphorylation sites (Ser 231 , Ser 660 and Ser 700 ) and one predicted Akt phosphorylation site (Thr 590 ) in control mice, AMPKα2 inactive transgenic mice (AMPKα2i TG) and Akt2-knockout mice (Akt2 KO...

View articletitled, Contraction regulates site-specific phosphorylation of TBC1D1 in skeletal muscle

Includes: Supplementary data

Articles

Role of phosphoinositide 3-kinase β in platelet aggregation and thromboxane A 2 generation mediated by G i signalling pathways

Analia Garcia, Soochong Kim, Kamala Bhavaraju, Simone M. Schoenwaelder, Satya P. Kunapuli

Biochem J (2010) 429 (2): 369–377.

https://doi.org/10.1042/BJ20100166

Published: 28 June 2010

... responses in platelets from P2Y 1 −/− mice. Finally, 2MeSADP (2-methyl-thio-ADP)-induced Akt phosphorylation was significantly inhibited in the presence of TGX-221, suggesting a critical role for PI3Kβ in G i -mediated signalling. Taken together, our results demonstrate that PI3Kβ plays an important role...

View articletitled, Role of phosphoinositide 3-kinase β in platelet aggregation and thromboxane A 2 generation mediated by G i signalling pathways

Articles

Molecular mechanisms of metabolic regulation by insulin in Drosophila

Aurelio A. Teleman

Biochem J (2010) 425 (1): 13–26.

https://doi.org/10.1042/BJ20091181

Published: 14 December 2009

... 2009 7 9 2009 © The Authors Journal compilation © 2010 Biochemical Society 2010 Akt Drosophila metabolism insulin signalling target of rapamycin (TOR) total body glucose total body lipid In the past decade, Drosophila has been one of the important model systems...

View articletitled, Molecular mechanisms of metabolic regulation by insulin in Drosophila

Articles

Elevated levels of IL-1β in Fanconi anaemia group A patients due to a constitutively active phosphoinositide 3-kinase-Akt pathway are capable of promoting tumour cell proliferation

Ana Ibáñez, Paula Río, José Antonio Casado, Juan Antonio Bueren, José Luis Fernández-Luna, Carlos Pipaón

Biochem J (2009) 422 (1): 161–170.

https://doi.org/10.1042/BJ20082118

Published: 29 July 2009

...-kinase)-Akt pathway in these cells. We provide evidence that the effect of Akt on IL-1β activation is mediated by the inhibition of GSK3β (glycogen synthase kinase 3β). Finally, our data indicate that the levels of IL-1β produced by FA-A lymphoblasts are enough to promote an activation of the cell cycle...

View articletitled, Elevated levels of IL-1β in Fanconi anaemia group A patients due to a constitutively active phosphoinositide 3-kinase-Akt pathway are capable of promoting tumour cell proliferation

Articles

At the crossroads of homoeostasis and disease: roles of the PACS proteins in membrane traffic and apoptosis

Robert T. Youker, Ujwal Shinde, Robert Day, Gary Thomas

Biochem J (2009) 421 (1): 1–15.

https://doi.org/10.1042/BJ20081016

Published: 12 June 2009

... in cancer and how viral pathogens ranging from HIV-1 to herpesviruses have evolved to usurp the PACS sorting machinery to promote virus assembly, viral spread and immunoevasion. Akt cancer furin herpesvirus HIV-1 Nef phosphofurin acidic cluster sorting (PACS)-1/2 polycystin-2 secretory pathway...

View articletitled, At the crossroads of homoeostasis and disease: roles of the PACS proteins in membrane traffic and apoptosis

Includes: Multimedia, Supplementary data

Articles

New anti-cancer role for PDK1 inhibitors: preventing resistance to tamoxifen

Christian Peifer, Dario R. Alessi

Biochem J (2009) 417 (1): e5–e7.

https://doi.org/10.1042/BJ20082243

Published: 12 December 2008

... are that PDK1 or PI3K (phosphoinositide 3-kinase), Akt (also known as protein kinase B), S6K (S6 kinase) and mTOR (mammalian target of rapamycin) inhibitors, already being developed for cancer therapy, are likely to have additional utility in sensitizing breast tumours to tamoxifen. In this commentary we also...

View articletitled, New anti-cancer role for PDK1 inhibitors: preventing resistance to tamoxifen

Articles

β-Arrestin1 interacts with the G-protein subunits β1γ2 and promotes β1γ2-dependent Akt signalling for NF-κB activation

Ming Yang, Rong L. He, Jeffrey L. Benovic, Richard D. Ye

Biochem J (2009) 417 (1): 287–296.

https://doi.org/10.1042/BJ20081561

Published: 12 December 2008

...-arrestin1 interacts with G β1γ2 derived from in vitro translation. Deletion mutagenesis of β-arrestin1 led to the identification of a region, comprising amino acids 181–280, as being responsible for its interaction with G β1γ2 . Overexpression of β-arrestin1 facilitates G β1γ2 -mediated Akt phosphorylation...

View articletitled, β-Arrestin1 interacts with the G-protein subunits β1γ2 and promotes β1γ2-dependent Akt signalling for NF-κB activation

Articles

mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1)

Juan M. García-Martínez, Dario R. Alessi

Biochem J (2008) 416 (3): 375–385.

https://doi.org/10.1042/BJ20081668

Published: 26 November 2008

... of S6K (S6 kinase), whereas mTORC2 (mTOR complex 2) phosphorylates the hydrophobic motif of Akt (also known as protein kinase B). In the present study we demonstrate that SGK1 hydrophobic motif phosphorylation and activity is ablated in knockout fibroblasts possessing mTORC1 activity, but lacking...

View articletitled, mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1)

Articles

Activation of hypoxia-inducible factor 1 in human T-cell leukaemia virus type 1-infected cell lines and primary adult T-cell leukaemia cells

Mariko Tomita, Gregg L. Semenza, Canine Michiels, Takehiro Matsuda, Jun-Nosuke Uchihara, Taeko Okudaira, Yuetsu Tanaka, Naoya Taira, Kazuiku Ohshiro, Naoki Mori

Biochem J (2007) 406 (2): 317–323.

https://doi.org/10.1042/BJ20070286

Published: 13 August 2007

... (phosphoinositide 3-kinase)/Akt signalling pathway, which is responsible for survival of HTLV-1-infected T-cells. HIFs (hypoxia-inducible factors) are transcriptional regulators that play a central role in the response to hypoxia. Overexpression of HIF-1α in many cancers is associated with a poor response...

View articletitled, Activation of hypoxia-inducible factor 1 in human T-cell leukaemia virus type 1-infected cell lines and primary adult T-cell leukaemia cells

Articles

Novel role for insulin as an autocrine growth factor for malignant brain tumour cells

Alexandre Arcaro, Kathrin T. Doepfner, Danielle Boller, Ana S. Guerreiro, Tarek Shalaby, Shaun P. Jackson, Simone M. Schoenwaelder, Olivier Delattre, Michael A. Grotzer, Barbara Fischer

Biochem J (2007) 406 (1): 57–66.

https://doi.org/10.1042/BJ20070309

Published: 26 July 2007

... with normal brain tissue, AT/RT cell lines overexpressed the IR (insulin receptor) and the IGFIR (insulin-like growth factor-I receptor). Moreover, insulin was secreted by AT/RT cells grown in serum-free medium. Insulin potently activated Akt (also called protein kinase B) in AT/RT cells, as compared...

View articletitled, Novel role for insulin as an autocrine growth factor for malignant brain tumour cells

Includes: Supplementary data

Articles

A WD-FYVE protein binds to the kinases Akt and PKCζ/λ

Thorsten Fritzius, Gabriela Burkard, Elvira Haas, Jochen Heinrich, Marc Schweneker, Magnus Bosse, Sven Zimmermann, Alexander D. Frey, Antje Caelers, Andre S. Bachmann, Karin Moelling

Biochem J (2006) 399 (1): 9–20.

https://doi.org/10.1042/BJ20060511

Published: 13 September 2006

... to the protein kinases Akt and PKCζ/λ (protein kinase Cζ/λ) via its WD-repeat propeller. ProF interacts more strongly with the kinases after hormonal stimulation. Endogenously expressed ProF and the two kinases interact in brain and in the preadipocyte cell line 3T3-L1, suggesting a role in secretory vesicular...

View articletitled, A WD-FYVE protein binds to the kinases Akt and PKCζ/λ

Includes: Multimedia, Supplementary data

Articles

Akt phosphorylates and suppresses the transactivation of retinoic acid receptor α

Harish Srinivas, Dianren Xia, Nicole L. Moore, Ivan P. Uray, Heetae Kim, Long Ma, Nancy L. Weigel, Powel H. Brown, Jonathan M. Kurie

Biochem J (2006) 395 (3): 653–662.

https://doi.org/10.1042/BJ20051794

Published: 11 April 2006

...) Mol. Cell. Biol. 25 , 1054–1069]. In the present study, we report that Akt, which is constitutively activated in NSCLC cells, phosphorylates RARα and inhibits its transactivation. Biochemical and functional analyses showed that Akt interacts with RARα and phosphorylates the Ser 96 residue of its DNA...

View articletitled, Akt phosphorylates and suppresses the transactivation of retinoic acid receptor α

Articles

Gα q binds to p110α/p85α phosphoinositide 3-kinase and displaces Ras

Lisa M. Ballou, Mohar Chattopadhyay, Yan Li, Suzanne Scarlata, Richard Z. Lin

Biochem J (2006) 394 (3): 557–562.

https://doi.org/10.1042/BJ20051493

Published: 24 February 2006

... Ras activation of the PI3K/Akt pathway but had no effect on Ras/Raf/MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase] signalling. These results suggest that activation of G q -coupled receptors leads to increased binding of Gα q ·GTP to some isoforms...

View articletitled, Gα q binds to p110α/p85α phosphoinositide 3-kinase and displaces Ras

Articles

Specific role for p85/p110β in GTP-binding-protein-mediated activation of Akt

Hiroshi Kubo, Kaoru Hazeki, Shunsuke Takasuga, Osamu Hazeki

Biochem J (2005) 392 (3): 607–614.

https://doi.org/10.1042/BJ20050671

Published: 06 December 2005

...Hiroshi Kubo; Kaoru Hazeki; Shunsuke Takasuga; Osamu Hazeki We prepared CHO (Chinese hamster ovary) cells expressing both IR (insulin receptor) and A 1 R (A 1 adenosine receptor). Treatment of the cells with insulin or PIA [ N 6 -(2-phenylisopropyl)adenosine], a specific A 1 R agonist increased Akt...

View articletitled, Specific role for p85/p110β in GTP-binding-protein-mediated activation of Akt

Articles

AS160, the Akt substrate regulating GLUT4 translocation, has a functional Rab GTPase-activating protein domain

Cristinel P. Mîinea, Hiroyuki Sano, Susan Kane, Eiko Sano, Mitsunori Fukuda, Johan Peränen, William S. Lane, Gustav E. Lienhard

Biochem J (2005) 391 (1): 87–93.

https://doi.org/10.1042/BJ20050887

Published: 26 September 2005

... that is phosphorylated on multiple sites by the protein kinase Akt. Phosphorylation of AS160 in adipocytes is required for insulin-stimulated translocation of the glucose transporter GLUT4 to the plasma membrane. The aim of the present study was to determine whether AS160 is in fact a GAP for Rabs, and, if so, what its...

View articletitled, AS160, the Akt substrate regulating GLUT4 translocation, has a functional Rab GTPase-activating protein domain

Articles

IGF-I stimulation of proteoglycan synthesis by chondrocytes requires activation of the PI 3-kinase pathway but not ERK MAPK

Bela G. Starkman, John D. Cravero, Marcello Delcarlo, Jr, Richard F. Loeser

Biochem J (2005) 389 (3): 723–729.

https://doi.org/10.1042/BJ20041636

Published: 26 July 2005

... LY294002 and wortmannin blocked IGF-I-stimulated Akt phosphorylation without blocking ERK phosphorylation and this was associated with complete inhibition of proteoglycan synthesis. A decrease in IGF-I-stimulated proteoglycan synthesis was also observed upon inhibition of mTOR (mammalian target...

View articletitled, IGF-I stimulation of proteoglycan synthesis by chondrocytes requires activation of the PI 3-kinase pathway but not ERK MAPK

Articles

Identification and characterization of pleckstrin-homology-domain-dependent and isoenzyme-specific Akt inhibitors

Stanley F. BARNETT, Deborah DEFEO-JONES, Sheng FU, Paula J. HANCOCK, Kathleen M. HASKELL, Raymond E. JONES, Jason A. KAHANA, Astrid M. KRAL, Karen LEANDER, Ling L. LEE, John MALINOWSKI, Elizabeth M. McAVOY, Debbie D. NAHAS, Ronald G. ROBINSON, Hans E. HUBER

Biochem J (2005) 385 (2): 399–408.

https://doi.org/10.1042/BJ20041140

Published: 07 January 2005

... (homogeneous time-resolved fluorescence) assay for Akt kinase activity and screened approx. 270000 compounds for their ability to inhibit the three isoforms of Akt. Two Akt inhibitors were identified that exhibited isoenzyme specificity. The first compound (Akt-I-1) inhibited only Akt1 (IC 50 4.6 μM) while...

View articletitled, Identification and characterization of pleckstrin-homology-domain-dependent and isoenzyme-specific Akt inhibitors

Articles

C-terminal fragment of tetanus toxin heavy chain activates Akt and MEK/ERK signalling pathways in a Trk receptor-dependent manner in cultured cortical neurons

Carles GIL, Imane CHAIB-OUKADOUR, José AGUILERA

Biochem J (2003) 373 (2): 613–620.

https://doi.org/10.1042/bj20030333

Published: 15 July 2003

... neurotrophin Trk receptor, Akt kinase and ERK pathway, in cultured cortical neurons from foetal rat brain, by tetanus toxin (TeTx) as well as by the C-terminal part of its heavy chain (H C -TeTx). TeTx and H C -TeTx induce fast and transient phosphorylation of Trk receptor at Tyr 674 and Tyr 675...

View articletitled, C-terminal fragment of tetanus toxin heavy chain activates Akt and MEK/ERK signalling pathways in a Trk receptor-dependent manner in cultured cortical neurons

Articles

Regulation of insulin signal transduction pathway by a small-molecule insulin receptor activator

Victor D.H. DING, Sajjad A. QURESHI, Deborah SZALKOWSKI, Zhihua LI, Dawn E. BIAZZO-ASHNAULT, Dan XIE, Kun LIU, A. Brian JONES, David E. MOLLER, Bei B. ZHANG

Biochem J (2002) 367 (1): 301–306.

https://doi.org/10.1042/bj20020708

Published: 01 October 2002

... phosphorylation of Akt, the 70kDa ribosomal protein S6 kinase and glycogen synthase-3 (deactivation) in Chinese-hamster ovary cells expressing human IR. Similar to insulin, compound 2 stimulated glucose uptake, glycogen synthesis and inhibited isoprenaline-stimulated lipolysis in adipocytes. A structurally...

View articletitled, Regulation of insulin signal transduction pathway by a small-molecule insulin receptor activator

Articles

Nitric oxide regulates oestrogen-activated signalling pathways at multiple levels through cyclic GMP-dependent recruitment of insulin receptor substrate 1

Sestina FALCONE, Loredana MAURO, Giacinta de ROSE, Clara PAOLUCCI, Clara SCIORATI, Sebastiano ANDO, Emilio CLEMENTI

Biochem J (2002) 366 (1): 165–173.

https://doi.org/10.1042/bj20020017

Published: 15 August 2002

... the insulin receptor substrate-1, with recruitment to this adapter of the phosphatidylinositol 3′-kinase and persistent activation of Akt (protein kinase B). Active Akt, in turn, prevented E 2 from activating p42/44 extracellular signal-regulated kinases (ERK 1/2). These effects of NO, which were mediated...

View articletitled, Nitric oxide regulates oestrogen-activated signalling pathways at multiple levels through cyclic GMP-dependent recruitment of insulin receptor substrate 1

Articles

The kinase DYRK1A phosphorylates the transcription factor FKHR at Ser329 in vitro, a novel in vivo phosphorylation site

Yvonne L. WOODS, Graham RENA, Nick MORRICE, Andreas BARTHEL, Walter BECKER, Shaodong GUO, Terry G. UNTERMAN, Philip COHEN

Biochem J (2001) 355 (3): 597–607.

https://doi.org/10.1042/bj3550597

Published: 24 April 2001

... at Ser 329 in vivo . 1 To whom correspondence should be addressed (e-mail [email protected] ). 13 12 2000 5 2 2001 27 2 2001 The Biochemical Society, London © 2001 2001 Akt apoptosis insulin action gene transcription protein kinase B Biochem. J. (2001) 355...

View articletitled, The kinase DYRK1A phosphorylates the transcription factor FKHR at Ser329 in vitro, a novel in vivo phosphorylation site

Articles

Ceramide dissociates 3′-phosphoinositide production from pleckstrin homology domain translocation

Suzanne STRATFORD, Daryll B. DEWALD, Scott A. SUMMERS

Biochem J (2001) 354 (2): 359–368.

https://doi.org/10.1042/bj3540359

Published: 22 February 2001

... several PI-3K-dependent events, including insulin-stimulated glucose uptake and growth-factor-stimulated cell survival. Here we show that ceramide analogues specifically prevent the recruitment of the PtdIns(3,4,5) P 3 -binding proteins Akt/protein kinase B (PKB) or the general receptor...

View articletitled, Ceramide dissociates 3′-phosphoinositide production from pleckstrin homology domain translocation

Articles

Divergence in the anti-apoptotic signalling pathways used by nerve growth factor and basic fibroblast growth factor (bFGF) in PC12 cells: rescue by bFGF involves protein kinase Cδ

Maribeth M. WERT, H. Clive PALFREY

Biochem J (2000) 352 (1): 175–182.

https://doi.org/10.1042/bj3520175

Published: 07 November 2000

...Maribeth M. WERT; H. Clive PALFREY The mechanisms whereby nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) block apoptosis in serum-deprived PC12 cells were investigated. NGF, but not bFGF, strongly activated Akt/protein kinase B, a downstream effector of phosphoinositide...

View articletitled, Divergence in the anti-apoptotic signalling pathways used by nerve growth factor and basic fibroblast growth factor (bFGF) in PC12 cells: rescue by bFGF involves protein kinase Cδ

Articles

The PI3K–PDK1 connection: more than just a road to PKB

Bart VANHAESEBROECK, Dario R. ALESSI

Biochem J (2000) 346 (3): 561–576.

https://doi.org/10.1042/bj3460561

Published: 07 March 2000

... is the protein kinase Akt or protein kinase B (PKB). In quiescent cells, PKB resides in the cytosol in a low-activity conformation. Upon cellular stimulation, PKB is activated through recruitment to cellular membranes by PI3K lipid products and phosphorylation by 3ʹ-phosphoinositide-dependent kinase-1 (PDK1...

View articletitled, The PI3K–PDK1 connection: more than just a road to PKB

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