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. 1998 Dec 8;95(25):14950-5.
doi: 10.1073/pnas.95.25.14950.

The akt kinase: molecular determinants of oncogenicity

M Aoki  1 , O Batista, A Bellacosa, P Tsichlis, P K Vogt
Affiliations

The akt kinase: molecular determinants of oncogenicity

M Aoki et al. Proc Natl Acad Sci U S A. .

Abstract

The serine-threonine kinase Akt is a downstream target of phosphoinositide 3-kinase (PI 3-kinase); it is activated by the phosphoinositide 3-phosphate-dependent kinases PDK1 and PDK2. Certain mutated forms of Akt induce oncogenic transformation in chicken embryo fibroblast cultures and hemangiosarcomas in young chickens. This ability to transform cells depends on localization of Akt at the plasma membrane and on the kinase activity of Akt. A transdominant negative form of Akt interferes with oncogenic transformation induced by the p3k oncogene, which codes for an activated form of PI 3-kinase. Akt is therefore an essential mediator of p3k-induced oncogenicity.

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Figures

Figure 1
Figure 1
Schematic structures of Akt constructs. Group-specific antigen (Gag) sequence in v-Akt or myristylation signals are highlighted as black boxes. Functionally important amino acid residues in the PH and kinase domains are noted. The HA epitope tag is on the amino terminus of constructs 1 and 4–8; on all others, it is on the carboxyl terminus.
Figure 2
Figure 2
Morphology of CEF transfected with Akt constructs. (A) RCAS vector control. (B) c-Akt. (C) v-Akt. (D) Akt-E40K. (E) Akt-Myr. (F) Akt-K179M. (G and H) Phase-contrast micrographs of CEFs transfected with Akt-Myr (G) or RCAS vector (H).
Figure 3
Figure 3
Subcellular localization of the HA-tagged Akt proteins in CEF. (A) RCAS vector control. (B) c-Akt. (C) v-Akt. (D) Akt-E40K. (E) Akt-Myr. (F) Akt-K179M.
Figure 4
Figure 4
Expression and in vitro kinase activity of Akt proteins. (A and C) Lysates of CEF stably transfected with HA-tagged Akt were probed with anti-HA antibody in Western blots. (B and D) In vitro immune complex kinase assay of the HA-tagged Akt constructs with histone H2B as substrate.
Figure 5
Figure 5
Akt and cellular signaling. See text for details.
See this image and copyright information in PMC

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