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Literature DB >> 11544177

Growth retardation and increased apoptosis in mice with homozygous disruption of the Akt1 gene.

W S Chen¹, P Z Xu, K Gottlob, M L Chen, K Sokol, T Shiyanova, I Roninson, W Weng, R Suzuki, K Tobe, T Kadowaki, N Hay.

Abstract

The serine/threonine kinase Akt has been implicated in the control of cell survival and metabolism. Here we report the disruption of the most ubiquitously expressed member of the akt family of genes, akt1, in the mouse. Akt1(-/-) mice are viable but smaller when compared to wild-type littermates. In addition, the life span of Akt1(-/-) mice, upon exposure to genotoxic stress, is shorter. However, Akt1(-/-) mice do not display a diabetic phenotype. Increased spontaneous apoptosis in testes, and attenuation of spermatogenesis is observed in Akt1(-/-) male mice. Increased spontaneous apoptosis is also observed in the thymi of Akt1(-/-) mice, and Akt1(-/-) thymocytes are more sensitive to apoptosis induced by gamma-irradiation and dexamethasone. Finally, Akt1(-/-) mouse embryo fibroblasts (MEFs) are more susceptible to apoptosis induced by TNF, anti-Fas, UV irradiation, and serum withdrawal.

Entities: Chemical Disease Gene Species

Mesh：

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Year: 2001 PMID： 11544177 PMCID： PMC312770 DOI： 10.1101/gad.913901

Source DB: PubMed Journal: Genes Dev ISSN： 0890-9369 Impact factor: 11.361

39 in total

Review 1. Cellular survival: a play in three Akts.

Authors: S R Datta; A Brunet; M E Greenberg
Journal: Genes Dev Date: 1999-11-15 Impact factor: 11.361

2. Kit/stem cell factor receptor-induced activation of phosphatidylinositol 3'-kinase is essential for male fertility.

Authors: P Blume-Jensen; G Jiang; R Hyman; K F Lee; S O'Gorman; T Hunter
Journal: Nat Genet Date: 2000-02 Impact factor: 38.330

3. Drosophila tumor suppressor PTEN controls cell size and number by antagonizing the Chico/PI3-kinase signaling pathway.

Authors: D C Goberdhan; N Paricio; E C Goodman; M Mlodzik; C Wilson
Journal: Genes Dev Date: 1999-12-15 Impact factor: 11.361

9. Regulation of the activity of p38 mitogen-activated protein kinase by Akt in cancer and adenoviral protein E1A-mediated sensitization to apoptosis.

Authors: Yong Liao; Mien-Chie Hung
Journal: Mol Cell Biol Date: 2003-10 Impact factor: 4.272

10. The Akt1 isoform is required for optimal IFN-β transcription through direct phosphorylation of β-catenin.

Authors: Benjamin N Gantner; Huali Jin; Feng Qian; Nissim Hay; Bin He; Richard D Ye
Journal: J Immunol Date: 2012-08-17 Impact factor: 5.422

Growth retardation and increased apoptosis in mice with homozygous disruption of the Akt1 gene.

Review 1. Cellular survival: a play in three Akts.

2. Kit/stem cell factor receptor-induced activation of phosphatidylinositol 3'-kinase is essential for male fertility.

3. Drosophila tumor suppressor PTEN controls cell size and number by antagonizing the Chico/PI3-kinase signaling pathway.

Review 4. The regulation and activities of the multifunctional serine/threonine kinase Akt/PKB.

5. Cell-autonomous regulation of cell and organ growth in Drosophila by Akt/PKB.

6. Drosophila PTEN regulates cell growth and proliferation through PI3K-dependent and -independent pathways.

7. Regulation of GLUT1 gene transcription by the serine/threonine kinase Akt1.

8. PIK3CA is implicated as an oncogene in ovarian cancer.

9. PTEN affects cell size, cell proliferation and apoptosis during Drosophila eye development.

10. Protein kinase B regulates T lymphocyte survival, nuclear factor kappaB activation, and Bcl-X(L) levels in vivo.

1. Akt/PKB regulates laminin and collagen IV isotypes of the basement membrane.

Review 2. Tissue-specific targeting of the insulin receptor gene.

3. Interferons mediate terminal differentiation of human cortical thymic epithelial cells.

4. Activation of Akt/protein kinase B overcomes a G(2)/m cell cycle checkpoint induced by DNA damage.

5. Essential, nonredundant role for the phosphoinositide 3-kinase p110delta in signaling by the B-cell receptor complex.

6. Short-term akt activation in cardiac muscle cells improves contractile function in failing hearts.

Review 7. The PIK3CA gene as a mutated target for cancer therapy.

8. Conditional activation of akt in adult skeletal muscle induces rapid hypertrophy.

9. Regulation of the activity of p38 mitogen-activated protein kinase by Akt in cancer and adenoviral protein E1A-mediated sensitization to apoptosis.

10. The Akt1 isoform is required for optimal IFN-β transcription through direct phosphorylation of β-catenin.