Name=v-akt murine thymoma viral oncogene homolog 1

Name=v-akt murine thymoma viral oncogene homolog 2

Name=v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma)


Akt1, also known as "Akt" or protein kinase B (PKB) is an important molecule in mammalian cellular signaling.

AKT family: AKT1, AKT2, AKT3

In humans, there are three genes in the "Akt family": Akt1, Akt2, and Akt3. These genes code for enzymes that are members of the serine/threonine-specific protein kinase family (EC number|

Akt1 is involved in cellular survival pathways, by inhibiting apoptotic processes. Akt1 is also able to induce protein synthesis pathways, and is therefore a key signaling protein in the cellular pathways that lead to skeletal muscle hypertrophy, and general tissue growth. Since it can block apoptosis, and thereby promote cell survival, Akt1 has been implicated as a major factor in many types of cancer. Akt (now also called Akt1) was originally identified as the oncogene in the transforming retrovirus, AKT8 by Dr. Philip Tsichlis at Fox Chase Cancer Center in the 1990's.

Akt2 is an important signaling molecule in the Insulin signaling pathway. It is required to induce glucose transport.

These separate roles for Akt1 and Akt2 were demonstrated by studying mice in which either the Akt1 or the Akt2 gene was deleted, or "knocked out". In a mouse which is null for Akt1 but normal for Akt2, glucose homeostasis is unperturbed, but the animals are smaller, consistent with a role for Akt1 in growth. In contrast, mice which do not have Akt2, but have normal Akt1, have mild growth deficiency and display a diabetic phenotype (insulin resistance), again consistent with the idea that Akt2 is more specific for the insulin receptor signaling pathway ref|Garofalo2003.

The role of Akt3 is less clear, though it appears to be predominantly expressed in brain. It has been reported that mice lacking Akt3 have small brains ref|Yang2004.

The name Akt does not refer to its function. Presumably, the "Ak" in Akt was a temporary classification name for a mouse strain developing spontaneous thymic lymphomas. The "t" stands for 'transforming', the letter was added when a transforming retrovirus was isolated from the Ak strain, which was termed "Akt-8". When the oncogene encoded in this virus was discovered, it was termed v-Akt. Thus, the later identified human analogues were named accordingly.

Regulation: Activation and Inactivation of Akt

Binding phospho-lipids in the membrane

Akt possesses a protein domain known as a PH domain, or Pleckstrin Homology domain, named after Pleckstrin, the protein in which it was first discovered. This domain binds to phosphoinositides with high affinity. In the case of the PH domain of Akt, it binds either phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)"P"3 aka PIP3) or phosphatidylinositol (3,4)-bisphosphate (PtdIns(3,4)"P"2 aka PI(3,4)P2). This is useful for control of cellular signaling because the di-phosphorylated phosphoinositide PtdIns(4,5)P2 is only phosphorylated by the family of enzymes, PI 3-kinases (phosphoinositide 3-kinase or PI3K), and only upon receipt of chemical messengers which tell the cell to begin the growth process. For example, PI 3-kinases may be activated by a G protein coupled receptor or receptor tyrosine kinase such as the insulin receptor. Once activated, PI 3-kinases phosphorylates PtdIns(4,5)P2 to form PtdIns(3,4,5)P3.

Phosphorylation by PDK1 and PDK2

Once correctly positioned in the membrane via binding of PIP3, Akt can then be phosphorylated by its activating kinases, phosphoinositide dependent kinase 1 (PDPK1 at threonine 308) and mTORC2 (at serine 473). First, the mammalian target of rapamycin complex 2 (mTORC2); mTORC2 therefore functionally acts as the long-sought PDK2 molecule, although other molecules, including Integrin-Linked Kinase (ILK) and Mitogen-Activated Protein Kinase Activated Protein Kinase-2 (MAPKAPK2) can also serve as PDK2. Phosphorylation by mTORC2 stimulates the subsequent phosphorylation of Akt by PDK1. Activated Akt can then go on to activate or deactivate its myriad substrates via its kinase activity. See this link for a more thorough and detailed image of the [http://www.cellsignal.com/pathways/akt-signaling.jsp Akt signaling pathway] .

Besides being a downstream effector of PI 3-kinases, Akt may also be activated in a PI 3-kinase-independent manner. Studies have suggested that cAMP-elevating agents could activate Akt through protein kinase A (PKA), although these studies are disputed and the mechanism of action is unclear.

Lipid phosphatases control the amount of PIP3, thereby modulating the ability of Akt to be activated

PI3K dependent Akt activation can be regulated through the tumor suppressor PTEN, which works essentially as the opposite of PI3K mentioned above ( [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cooper.figgrp.2669 PTEN and PI3K] ). PTEN acts as a phosphatase to dephosphorylate PtdIns(3,4,5)P3 back to PtdIns(4,5)P2. This removes the membrane-localization factor from the Akt signaling pathway. Without this localization, the rate of Akt activation decreases significantly, as do the all the downstream pathways that depend on Akt for activation.

PIP3 can also be de-phosphorylated at the "5" position by the SHIP family of inositol phosphatases, SHIP1 and SHIP2. These poly-phosphate inositil phosphatases dephosphorylate PtdIns(3,4,5)P3 to form PtdIns(3,4)P2.

Protein phosphatases control the amount of phosphorylated Akt

The phosphatases in the PHLPP family, PHLPP1 and PHLPP2 have been shown to directly de-phosphorylate, and therefore inactivate, distinct Akt isoforms. PHLPP2 dephosphorylates Akt1 and Akt3, whereas PHLPP1 is specific for Akt 2 and Akt3.


Akt regulates cellular survival ref|Song2005 and metabolism by binding and regulating many downstream effectors, e.g. Nuclear Factor-κB, Bcl-2 family proteins and murine double minute 2 (MDM2).

Cell survival

Akt could promote growth factor-mediated cell survival both directly and indirectly. BAD is a pro-apoptotic protein of the Bcl-2 family. Akt could phosphorylate BAD on Ser136 ( [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.figgrp.2865 BAD phosphorylation by Akt)] , which makes BAD dissociate from the Bcl-2/Bcl-X complex and lose the pro-apoptotic function ( [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mcb.figgrp.6902 BAD interaction with Bcl-2] ). Akt could also activate NF-κB via regulating IκB kinase (IKK), thus result in transcription of pro-survival genes ( [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=eurekah.figgrp.997 regulation of NF-kB] ).

Cell Cycle

Akt is known to play a role in cell cycle. Under various circumstances, activation of Akt was shown to overcome cell cycle arrest in G1ref|Ramaswamy1999 and G2ref|Kandel2001 phases. Moreover, activated Akt may enable proliferation and survival of cells that have sustained a potentially mutagenic impact and, therefore, may contribute to acquisition of mutations in other genes.


Akt2 is required for the insulin-induced translocation of glucose transporter 4 (GLUT4) to the plasma membrane. Glycogen synthase kinase 3 (GSK-3) could be inhibited upon phosphorylation by Akt, which results in promotion of glycogen synthesis. GSK3 is also involved in Wnt signaling cascade, so Akt might be also implicated in the Wnt pathway.Still unknown role in HCV induced steatosis.


Akt1 has also been implicated in angiogenesis and tumor development. Deficiency of Akt1 in mice although inhibited physiological angiogenesis, it enhanced pathological angiogenesis and tumor growth associated with matrix abnormalities in skin and blood vessels ref|Chen2005,ref|Somanath2006


#Robert S. Garofalo, Stephen J. Orena, Kristina Rafidi, Anthony J. Torchia, Jeffrey L. Stock, Audrey L. Hildebrandt, Timothy Coskran, Shawn C. Black, Dominique J. Brees, Joan R. Wicks, John D. McNeish, and Kevin G. Coleman (2003) "Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKB beta" "Journal of Clinical Investigation" Volume 112, pages 197-208. [http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=12843127 full text online] Entrez Pubmed|12843127
# Z. Z. Yang, O. Tschopp, A. Baudry, B. Dummler, D. Hynx and B. A. Hemmings. (2004) Physiological functions of protein kinase B/Akt. "Biochem Soc Trans." 32:350-354. Review. [http://www.biochemsoctrans.org/bst/032/0350/bst0320350.htm full text online] Entrez Pubmed|15046607
# Gang Song, Gaoliang Ouyang and Shideng Bao. (2005) The activation of Akt/PKB signaling pathway and cell survival. "J. Cell. Mol. Med." 9:59-71. [http://www.jcmm.org/en/pdf/9/1/jcmm009.001.07.pdf Download full text] (PDF format).
# Ramaswamy S, Nakamura N, Vazquez F, Batt DB, Perera S, Roberts TM, Sellers WR 1999 Regulation of G1 progression by the PTEN tumor suppressor protein is linked to inhibition of the phosphatidylinositol 3-kinase/Akt pathway. Proc Natl Acad Sci U S A 96:2110-2115. Entrez Pubmed|12391152
# Kandel ES, Skeen J, Majewski N, Di Cristofano A, Pandolfi PP, Feliciano CS, Gartel A, Hay N 2002 Activation of Akt/protein kinase B overcomes a G(2)/m cell cycle checkpoint induced by DNA damage. Mol Cell Biol 22:7831-7841. Entrez Pubmed|10051603
# Chen J, Somanath PR, Razorenova O, Chen WS, Hay N, Bornstein P, Byzova TV. Akt1 regulates pathological angiogenesis, vascular maturation and permeability in vivo. Nat Med. 2005 Nov;11(11):1188-96.
# Somanath PR, Razorenova OV, Chen J, Byzova TV. Akt1 in endothelial cell and angiogenesis. Cell Cycle. 2006 Mar;5(5):512-8.

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  • Akt — (von lat. agere „handeln“; Partizip „actum“ „das Gemachte“ oder actus, actio „Tat“) bezeichnet: allgemein einen Vorgang, eine Handlung, siehe Handeln die realisierte Wirklichkeit im Gegensatz zur Potenz, der (noch) nicht realisierten Möglichkeit …   Deutsch Wikipedia

  • AKT — (von lat. agere „handeln“; Partizip „actum“ „das Gemachte“ oder actus, actio „Tat“) bezeichnet: allgemein einen Vorgang, eine Handlung, siehe Handeln die realisierte Wirklichkeit im Gegensatz zur Potenz, der (noch) nicht realisierten Möglichkeit …   Deutsch Wikipedia

  • akt — I {{/stl 13}}{{stl 8}}rz. mnż I, D. u, Mc. akcie {{/stl 8}}{{stl 20}} {{/stl 20}}{{stl 12}}1. {{/stl 12}}{{stl 7}} wykonanie, spełnienie czegoś; przejaw (jako objaw zewnętrzny lub proces wewnętrzny, psychiczny) : {{/stl 7}}{{stl 10}}Akt przemocy …   Langenscheidt Polski wyjaśnień

  • Akt — Ạkt 1. 〈m.; Gen.: (e)s, Pl.: en〉 = Akte 2. 〈m.; Gen.: (e)s, Pl.: e〉 a) Handlung, Vorgang, Tätigkeit, Tat; ein Akt der Menschlichkeit, Höflichkeit, Verzweiflung; ein symbolischer, feierlicher Akt b) Vorführung; ZirkusAkt c) Teil eines Bühnenwerkes …   Lexikalische Deutsches Wörterbuch

  • Akt — Cette page d’homonymie répertorie les différents sujets et articles partageant un même nom. {{{image}}}   Sigles d une seule lettre   Sigles de deux lettres > Sigles de trois lettres …   Wikipédia en Français

  • Akt — Akt: Das Mitte des 15. Jh.s entlehnte Fremdwort, das auf lat. actus »Handlung; Geschehen; Darstellung; Vorgang usw.« zurückgeht (zu lat. agere, actum »treiben; handeln, tätig sein usw.«, vgl. ↑ agieren), erscheint zuerst mit der allgemeinen Bed.… …   Das Herkunftswörterbuch

  • AKT — motos antes Ensambladora Corbeta S.A. es una empresa colombiana ensambladora de motocicletas, filial del grupo ALKOSTO (Colombiana de COmercio S.A.), con sede principal en la ciudad de Envigado, en Antioquia (Colombia), que produce una serie de… …   Wikipedia Español

  • Akt — (lat.), im allgemeinen Handlung, Verrichtung, z. B. feierlicher A., A. der Gerechtigkeit; daher: von etwas A. nehmen, eine Sache zu Protokoll nehmen (um sie demnächst als Beweis zu gebrauchen), allgemein: sich etwas genau merken. – Insbesondere… …   Meyers Großes Konversations-Lexikon

  • Akt — [Basiswortschatz (Rating 1 1500)] Auch: • Tat • Handlung • Werk • Aufzug Bsp.: • Das war die Tat eines Narren. • …   Deutsch Wörterbuch

  • Akt — (lat.), Handlung, bes. feierliche und öffentliche; im Drama Hauptabschnitt der Handlung, s.v.w. Aufzug; in der bildenden Kunst die Stellung des nackten lebenden Modells und die danach gefertigte Zeichnung …   Kleines Konversations-Lexikon

  • Akt… — siehe auch Act… …   Universal-Lexikon

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