AKT1
Encyclopedia
RAC-alpha serine/threonine-protein kinase is an enzyme
that in humans is encoded by the AKT1 gene
. Multiple alternatively spliced transcript variants have been found for this gene.
-threonine
protein kinase
AKT1 is catalytically inactive in serum-starved primary and immortalized fibroblast
s. AKT1 and the related AKT2
are activated by platelet
-derived growth factor
. The activation is rapid and specific, and it is abrogated by mutations in the pleckstrin
homology
domain of AKT1. It was shown that the activation occurs through phosphatidylinositol 3-kinase. In the developing nervous system
AKT is a critical mediator of growth factor-induced neuronal survival. Survival factors can suppress apoptosis
in a transcription-independent manner by activating the serine/threonine kinase AKT1, which then phosphorylates and inactivates components of the apoptotic machinery. Mice lacking Akt1 display a 25% reduction in body mass, indicating that Akt1 is critical for transmitting growth promoting signals, most likely via the igf1
receptor. Mice lacking Akt1 are also resistant to cancer: they experience considerable delay in tumor growth initiated by the large T antigen or the Neu oncogene. A single-nucleotide polymorphism in this gene causes Proteus syndrome
.
in the transforming retrovirus
, AKT8. AKT8 was isolated from an AKR mouse spontaneous thymoma cell line by cocultivation with an indicator mink cell line. The transforming cellular sequences, v-akt, were cloned from a transformed mink cell clone and these sequences were used to identify Akt1 and Akt2 in a human clone library. AKT8 was isolated by Stephen Staal in the laboratory of Wallace P. Rowe; he subsequently cloned v-akt and human AKT1 and AKT2 while on staff at the Johns Hopkins Oncology Center.
In 2011, a mutation in AKT1 was strongly associated with Proteus syndrome, the disease which probably affected the Elephant Man
.
with Phosphoinositide-dependent kinase-1
, Keratin 10
, Integrin-linked kinase
, TSC2
, GAB2
, TRIB3
, NPM1
, BRCA1
, BRAF
, C-Raf
, MAPK14
, MARK2
, MAP2K4
, MTCP1
, TCL1A
, Nerve Growth factor IB
, MAPKAPK2
, PRKCQ
, Androgen receptor
, Heat shock protein 90kDa alpha (cytosolic), member A1, Plexin A1, MAP3K11
, TSC1
, MAP3K8
, Mammalian target of rapamycin
, PKN2
, AKTIP
, YWHAZ
, CHUK
and CDKN1B
.
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that in humans is encoded by the AKT1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. Multiple alternatively spliced transcript variants have been found for this gene.
Function
The serineSerine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
-threonine
Threonine
Threonine is an α-amino acid with the chemical formula HO2CCHCHCH3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as polar...
protein kinase
Protein kinase
A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins...
AKT1 is catalytically inactive in serum-starved primary and immortalized fibroblast
Fibroblast
A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for animal tissues, and plays a critical role in wound healing...
s. AKT1 and the related AKT2
AKT2
RAC-beta serine/threonine-protein kinase is an enzyme that in humans is encoded by the AKT2 gene.-Interactions:AKT2 has been shown to interact with TCL1A, APPL1, SH3RF1 and CHUK.-Further reading:...
are activated by platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
-derived growth factor
Growth factor
A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation. Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes....
. The activation is rapid and specific, and it is abrogated by mutations in the pleckstrin
Pleckstrin
Pleckstrin is a protein found in platelets. The name derives from platelet and leukocyte C kinase substrate and the KSTR string of amino acids.It is the source of the name pleckstrin homology domain....
homology
Homology (biology)
Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...
domain of AKT1. It was shown that the activation occurs through phosphatidylinositol 3-kinase. In the developing nervous system
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...
AKT is a critical mediator of growth factor-induced neuronal survival. Survival factors can suppress apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
in a transcription-independent manner by activating the serine/threonine kinase AKT1, which then phosphorylates and inactivates components of the apoptotic machinery. Mice lacking Akt1 display a 25% reduction in body mass, indicating that Akt1 is critical for transmitting growth promoting signals, most likely via the igf1
Insulin-like growth factor 1
Insulin-like growth factor 1 also known as somatomedin C is a protein that in humans is encoded by the IGF1 gene. IGF-1 has also been referred to as a "sulfation factor" and its effects were termed "nonsuppressible insulin-like activity" in the 1970s.IGF-1 is a hormone similar in molecular...
receptor. Mice lacking Akt1 are also resistant to cancer: they experience considerable delay in tumor growth initiated by the large T antigen or the Neu oncogene. A single-nucleotide polymorphism in this gene causes Proteus syndrome
Proteus syndrome
Proteus syndrome, also known as Wiedemann's syndrome , is a congenital disorder that causes skin overgrowth and atypical bone development, often accompanied by tumors over half the body....
.
History
Akt (now also called Akt1) was originally identified as the oncogeneOncogene
An oncogene is a gene that has the potential to cause cancer. In tumor cells, they are often mutated or expressed at high levels.An oncogene is a gene found in the chromosomes of tumor cells whose activation is associated with the initial and continuing conversion of normal cells into cancer...
in the transforming retrovirus
Retrovirus
A retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA...
, AKT8. AKT8 was isolated from an AKR mouse spontaneous thymoma cell line by cocultivation with an indicator mink cell line. The transforming cellular sequences, v-akt, were cloned from a transformed mink cell clone and these sequences were used to identify Akt1 and Akt2 in a human clone library. AKT8 was isolated by Stephen Staal in the laboratory of Wallace P. Rowe; he subsequently cloned v-akt and human AKT1 and AKT2 while on staff at the Johns Hopkins Oncology Center.
In 2011, a mutation in AKT1 was strongly associated with Proteus syndrome, the disease which probably affected the Elephant Man
Joseph Merrick
Joseph Carey Merrick , sometimes incorrectly referred to as John Merrick, was an English man with severe deformities who was exhibited as a human curiosity named the Elephant Man. He became well known in London society after he went to live at the London Hospital...
.
Interactions
AKT1 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with Phosphoinositide-dependent kinase-1
Phosphoinositide-dependent kinase-1
In the field of biochemistry, 3-phosphoinositide dependent protein kinase-1, also known as PDPK1 is a protein which in humans is encoded by the PDPK1 gene.PDPK1 is also known as "PDK1"...
, Keratin 10
Keratin 10
Keratin, type I cytoskeletal 10 also known as cytokeratin-10 or keratin-10 is a protein that in humans is encoded by the KRT10 gene. Keratin 10 is a type I keratin.- Function :...
, Integrin-linked kinase
Integrin-linked kinase
Integrin-linked kinase is a 59kDa protein originally identified while conducting a yeast-two hybrid screen with integrin β1 as the bait protein...
, TSC2
TSC2
Tuberous sclerosis protein 2, also known as TSC2 and Tuberin, is a human protein and gene.-Interactions:TSC2 has been shown to interact with FOXO1, GSK3B, Peptidylglycine alpha-amidating monooxygenase, RAP1A, MAPK1, AKT1, AXIN1, TSC1, PTK2, Protein kinase, AMP-activated, alpha 1, YWHAZ, RPS6KA1,...
, GAB2
GAB2
GRB2-associated-binding protein 2 is a protein that in humans is encoded by the GAB2 gene.The protein encoded by this gene, GAB2 is an adaptor protein serving as principal activator of Phosphatidylinositol 3-kinase...
, TRIB3
TRIB3
Tribbles homolog 3 is a protein that in humans is encoded by the TRIB3 gene.-Interactions:TRIB3 has been shown to interact with CSNK2B, TIAF1, RELA, MCM3AP, ATF5, Granulin, ATF4, AKT1, Fibronectin and SIAH1.-Further reading:...
, NPM1
NPM1
Nucleophosmin , also known as nucleolar phosphoprotein B23 or numatrin, is a protein that in humans is encoded by the NPM1 gene.- Function :...
, BRCA1
BRCA1
BRCA1 is a human caretaker gene that produces a protein called breast cancer type 1 susceptibility protein, responsible for repairing DNA. The first evidence for the existence of the gene was provided by the King laboratory at UC Berkeley in 1990...
, BRAF
BRAF (gene)
Serine/threonine-protein kinase B-Raf or simply B-Raf, also known as proto-oncogene B-Raf or v-Raf murine sarcoma viral oncogene homolog B1, is a protein that in humans is encoded by the BRAF gene...
, C-Raf
C-Raf
RAF proto-oncogene serine/threonine-protein kinase also known as proto-oncogene c-RAF or simply c-Raf is an enzyme that in humans is encoded by the RAF1 gene. The c-Raf protein functions in the MAPK/ERK signal transduction pathway as part of a protein kinase cascade...
, MAPK14
MAPK14
Mitogen-activated protein kinase 14, also called p38-α, is an enzyme that in humans is encoded by the MAPK14 gene.-Interactions:MAPK14 has been shown to interact with Casein kinase 2, alpha 1, RPS6KA4, MAPKAPK2, CDC25B, DUSP1, ZFP36L1, CDC25C, MAPKAPK3, Activating transcription factor 2, MAPK1,...
, MARK2
MARK2
Serine/threonine-protein kinase MARK2 is an enzyme that in humans is encoded by the MARK2 gene.-Further reading:...
, MAP2K4
MAP2K4
Dual specificity mitogen-activated protein kinase kinase 4 is an enzyme that in humans is encoded by the MAP2K4 gene.-Interactions:MAP2K4 has been shown to interact with FLNC, MAPK8, MAPK8IP3 and AKT1.-Further reading:...
, MTCP1
MTCP1
Protein p13 MTCP-1 is a protein that in humans is encoded by the MTCP1 gene.-Further reading:...
, TCL1A
TCL1A
T-cell leukemia/lymphoma protein 1A is a protein that in humans is encoded by the TCL1A gene.-Interactions:TCL1A has been shown to interact with AKT1 and AKT2.-Further reading:...
, Nerve Growth factor IB
Nerve Growth factor IB
The nerve Growth factor IB also known as Nur77 or NR4A1 is a protein that in humans is encoded by the NR4A1 gene....
, MAPKAPK2
MAPKAPK2
MAP kinase-activated protein kinase 2 is an enzyme that in humans is encoded by the MAPKAPK2 gene.-Interactions:MAPKAPK2 has been shown to interact with MAPK14, AKT1, PHC2 and SHC1.-Further reading:...
, PRKCQ
PRKCQ
Protein kinase C theta type is an enzyme that in humans is encoded by the PRKCQ gene.-Interactions:PRKCQ has been shown to interact with FYN, GLRX3, AKT1 and VAV1.PRKCQ has been shown to phosphorylate CARD11 as part of the NF-κB signaling pathway....
, Androgen receptor
Androgen receptor
The androgen receptor , also known as NR3C4 , is a type of nuclear receptor that is activated by binding of either of the androgenic hormones testosterone or dihydrotestosterone in the cytoplasm and then translocating into the nucleus...
, Heat shock protein 90kDa alpha (cytosolic), member A1, Plexin A1, MAP3K11
MAP3K11
Mitogen-activated protein kinase kinase kinase 11 is an enzyme that in humans is encoded by the MAP3K11 gene.-Interactions:MAP3K11 has been shown to interact with MAPK8IP1, CDC42, SH3RF1, MAPK8IP2 and AKT1.-Further reading:...
, TSC1
TSC1
Tuberous sclerosis protein 1, also known as TSC1 or hamartin, is a human protein and gene.- Function :This peripheral membrane protein was implicated as a tumor suppressor...
, MAP3K8
MAP3K8
Mitogen-activated protein kinase 8 is an enzyme that in humans is encoded by the MAP3K8 gene.-Interactions:MAP3K8 has been shown to interact with AKT1, CHUK, NFKB2 and NFKB1.-Further reading:...
, Mammalian target of rapamycin
Mammalian target of rapamycin
The mammalian target of rapamycin also known as mechanistic target of rapamycin or FK506 binding protein 12-rapamycin associated protein 1 is a protein which in humans is encoded by the FRAP1 gene...
, PKN2
PKN2
Serine/threonine-protein kinase N2 is an enzyme that in humans is encoded by the PKN2 gene.-Interactions:PKN2 has been shown to interact with Phosphoinositide-dependent kinase-1, AKT1, NCK1, PTPN13 and RHOA.-Further reading:...
, AKTIP
AKTIP
AKT-interacting protein is a protein that in humans is encoded by the AKTIP gene.- Molecular genetics :The association between the AKTIP gene variants in a sample of 273 bipolar patients using 3 single-nucleotide polymorphisms has been investigated...
, YWHAZ
YWHAZ
14-3-3 protein zeta/delta is a protein that in humans is encoded by the YWHAZ gene.-Interactions:YWHAZ has been shown to interact with TSC2, LIMK1, CDC25B, AKT1, BCAR1, Interleukin-9 receptor, C-Raf, HMGN1, Vimentin, Tau protein, Protein kinase Mζ, GP1BB, GP1BA, TNFAIP3, Bcl-2-associated death...
, CHUK
CHUK
Inhibitor of nuclear factor kappa-B kinase subunit alpha also known as IKK1 or conserved helix-loop-helix ubiquitous kinase is a protein kinase that in humans is encoded by the CHUK gene. IKK-α is part of the IκB kinase complex that plays an important role in regulating the NF-κB transcription...
and CDKN1B
CDKN1B
Cyclin-dependent kinase inhibitor 1B is an enzyme that in humans is encoded by the CDKN1B gene. It encodes a protein which belongs to the Cip/Kip family of cyclin dependent kinase inhibitor proteins. The encoded protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4...
.
See also
- AKTAKTAkt, also known as Protein Kinase B , is a serine/threonine protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, cell proliferation, apoptosis, transcription and cell migration.-Family members:...
- the AKT family of proteins - AKT2AKT2RAC-beta serine/threonine-protein kinase is an enzyme that in humans is encoded by the AKT2 gene.-Interactions:AKT2 has been shown to interact with TCL1A, APPL1, SH3RF1 and CHUK.-Further reading:...
- the gene for the second member of the AKT family - AKT3AKT3RAC-gamma serine/threonine-protein kinase is an enzyme that in humans is encoded by the AKT3 gene.-Interactions:AKT3 has been shown to interact with Protein kinase Mζ.-Further reading:...
- the gene for the third member of the AKT family