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Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...
s involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. PI3Ks are a family of related intracellular
signal transducer Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...
enzymes capable of phosphorylating the 3 position
hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydrox ...
group of the
inositol Inositol, or more precisely ''myo''-inositol, is a carbocyclic sugar that is abundant in the brain and other mammalian tissues; it mediates cell signal transduction in response to a variety of hormones, neurotransmitters, and growth factors an ...
ring of
phosphatidylinositol Phosphatidylinositol (or Inositol Phospholipid) consists of a family of lipids as illustrated on the right, where red is x, blue is y, and black is z, in the context of independent variation, a class of the phosphatidylglycerides. In such molecul ...
(PtdIns). The pathway, with
oncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.
PIK3CA and
tumor suppressor gene A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or re ...
PTEN, is implicated in the sensitivity of cancer tumors to
insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabol ...
and
IGF1 Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in molecular structure to insulin which plays an important role in childhood growth, and has anabolic effects in adults. IGF-1 is a protein that in humans ...
, and in
calorie restriction Calorie restriction (caloric restriction or energy restriction) is a dietary regimen that reduces intake of energy from caloric foods & beverages without incurring malnutrition. "Reduce" can be defined relative to the subject's previous intake be ...
.


Discovery

The discovery of PI3Ks by Lewis Cantley and colleagues began with their identification of a previously unknown phosphoinositide kinase associated with the
polyoma ''Polyomaviridae'' is a family of viruses whose natural hosts are primarily mammals and birds. As of 2020, there are six recognized genera and 117 species, five of which are unassigned to a genus. 14 species are known to infect humans, while othe ...
middle T protein. They observed unique substrate specificity and chromatographic properties of the products of the lipid kinase, leading to the discovery that this phosphoinositide kinase had the unprecedented ability to phosphorylate phosphoinositides on the 3' position of the inositol ring. Subsequently, Cantley and colleagues demonstrated that in vivo the enzyme prefers PtdIns(4,5)P2 as a substrate, producing the novel phosphoinositide PtdIns(3,4,5)P3 previously identified in neutrophils.


Classes

The PI3K family is divided into four different classes: Class I, Class II, Class III, and Class IV. The classifications are based on primary structure, regulation, and ''in vitro'' lipid substrate specificity.


Class I

Class I PI3Ks catalyze the conversion of phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2) into
phosphatidylinositol (3,4,5)-trisphosphate Phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)''P''3), abbreviated PIP3, is the product of the class I phosphoinositide 3-kinases (PI 3-kinases) phosphorylation of phosphatidylinositol (4,5)-bisphosphate (PIP2). It is a phospholipid th ...
(PI(3,4,5)P3) in vivo. While in vitro, they have also been shown to convert
phosphatidylinositol Phosphatidylinositol (or Inositol Phospholipid) consists of a family of lipids as illustrated on the right, where red is x, blue is y, and black is z, in the context of independent variation, a class of the phosphatidylglycerides. In such molecul ...
(PI) into phosphatidylinositol 3-phosphate (PI3P) and
phosphatidylinositol 4-phosphate Phosphatidylinositol-4-phosphate (PtdIns4''P'', PI-4-P, PI4P, or PIP) is a precursor of phosphatidylinositol (4,5)-bisphosphate. PtdIns4''P'' is prevalent in the membrane of the Golgi apparatus. In the Golgi apparatus, PtdIns4''P'' binds to the GT ...
(PI4P) into
phosphatidylinositol (3,4)-bisphosphate Phosphatidylinositol (3,4)-bisphosphate (PtdIns(3,4)''P''2) is a minor phospholipid component of cell membranes, yet an important second messenger. The generation of PtdIns(3,4)''P''2 at the plasma membrane activates a number of important cell sig ...
(PI(3,4)P2), these reactions are strongly disfavoured in vivo. The PI3K is activated by
G protein-coupled receptors G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...
and
tyrosine kinase receptors Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase ...
. Class I PI3Ks are heterodimeric molecules composed of a regulatory and a catalytic
subunit Subunit may refer to: *Subunit HIV vaccine, a class of HIV vaccine *Protein subunit, a protein molecule that assembles with other protein molecules *Monomer, a molecule that may bind chemically to other molecules to form a polymer *Sub-subunit, a ...
; they are further divided between IA and IB subsets on sequence similarity. Class IA PI3Ks are composed of a heterodimer between a p110 catalytic subunit and a shorter regulatory subunit (often p85). There are five variants of the regulatory subunit: the three splice variants p85α, p55α, and p50α, p85β, and p55γ. There are also three variants of the p110 catalytic subunit designated p110α, β, or δ catalytic subunit. The first three regulatory subunits are all splice variants of the same gene (''Pik3r1''), the other two being expressed by other genes (Pik3r2 and Pik3r3, p85β, and p55γ, respectively). The most highly expressed regulatory subunit is p85α; all three catalytic subunits are expressed by separate genes (''Pik3ca'', ''Pik3cb'', and ''Pik3cd'' for
p110α The phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (the HUGO-approved official symbol = PIK3CA; HGNC ID, HGNC:8975), also called p110α protein, is a class I PI 3-kinase catalytic subunit. The human p110α protein is enco ...
,
p110β Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta isoform is an enzyme that in humans is encoded by the ''PIK3CB'' gene. Phosphoinositide 3-kinases (PI3Ks) phosphorylate the 3-prime OH position of the inositol ring of inositol ...
, and p110δ, respectively). The first two p110 isoforms (α and β) are expressed in all cells, but p110δ is expressed primarily in
leukocytes White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mul ...
, and it has been suggested that it evolved in parallel with the adaptive immune system. The regulatory p101 and catalytic
p110γ Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform is an enzyme that in humans is encoded by the ''PIK3CG'' gene. Function This gene encodes a protein that belongs to the pi3/pi4-kinase family of proteins. The gene p ...
subunits comprise the class IB PI3Ks and are encoded by a single gene each (''Pik3cg'' for
p110γ Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform is an enzyme that in humans is encoded by the ''PIK3CG'' gene. Function This gene encodes a protein that belongs to the pi3/pi4-kinase family of proteins. The gene p ...
and ''Pik3r5'' for p101). The p85 subunits contain SH2 and SH3 domains (). The SH2 domains bind preferentially to phosphorylated tyrosine residues in the amino acid sequence context Y-X-X-M.


Classes II and III

Class II and
III III or iii may refer to: Companies * Information International, Inc., a computer technology company * Innovative Interfaces, Inc., a library-software company * 3i, formerly Investors in Industry, a British investment company Other uses * Ins ...
PI3Ks are differentiated from the Class I by their structure and function. The distinct feature of Class II PI3Ks is the C-terminal C2 domain. This domain lacks critical
Asp Asp may refer to: Places * Asp, part of Densbüren, Aargau, Switzerland * Aspe (''Asp'' in Valencian), Alicante, Spain * Asp Lake, a lake in Minnesota Animals * Asp (fish) * Asp (snake), in antiquity, one of several venomous snakes ** ''Cera ...
residues to coordinate binding of Ca2+, which suggests class II PI3Ks bind lipids in a Ca2+-independent manner. Class II comprises three catalytic isoforms (C2α, C2β, and C2γ), but, unlike Classes I and III, no regulatory proteins. Class II catalyse the production of PI(3)P from PI and PI(3,4)P2 from PI(4)P; however, little is known about their role in immune cells. PI(3,4)P2 has, however, been shown to play a role in the invagination phase of clathrin-mediated endocytosis. C2α and C2β are expressed through the body, but expression of C2γ is limited to
hepatocytes A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, bi ...
. Class III PI3Ks produce only PI(3)P from PI but are more similar to Class I in structure, as they exist as heterodimers of a catalytic ( Vps34) and a regulatory (Vps15/p150) subunits. Class III seems to be primarily involved in the trafficking of proteins and vesicles. There is, however, evidence to show that they are able to contribute to the effectiveness of several process important to immune cells, not least
phagocytosis Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis i ...
.


Class IV

A group of more distantly related enzymes is sometimes referred to as class IV PI3Ks. It is composed of
ataxia telangiectasia mutated ATM serine/threonine kinase or Ataxia-telangiectasia mutated, symbol ATM, is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks. It phosphorylates several key proteins that initiate activation of the DNA ...
(ATM),
ataxia telangiectasia and Rad3 related Serine/threonine-protein kinase ATR also known as ataxia telangiectasia and Rad3-related protein (ATR) or FRAP-related protein 1 (FRP1) is an enzyme that, in humans, is encoded by the ''ATR'' gene. It is a large kinase of about 301.66 kDa. ATR bel ...
(ATR), DNA-dependent protein kinase (DNA-PK) and
mammalian target of rapamycin The mammalian target of rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the ''MTOR'' gene. ...
(mTOR). They are protein serine/threonine kinases.


Human genes


Mechanism

The various 3-phosphorylated
phosphoinositides Phosphatidylinositol (or Inositol Phospholipid) consists of a family of lipids as illustrated on the right, where red is x, blue is y, and black is z, in the context of independent variation, a class of the phosphatidylglycerides. In such molecul ...
that are produced by PI3Ks (
PtdIns3P Phosphatidylinositol 3-phosphate (PtdIns3''P'') is a phospholipid found in cell membranes that helps to recruit a range of proteins, many of which are involved in protein trafficking, to the membranes. It is the product of both the class II and II ...
,
PtdIns(3,4)P2 Phosphatidylinositol (3,4)-bisphosphate (PtdIns(3,4)''P''2) is a minor phospholipid component of cell membranes, yet an important second messenger. The generation of PtdIns(3,4)''P''2 at the plasma membrane activates a number of important cell sig ...
,
PtdIns(3,5)P2 Phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) is one of the seven phosphoinositides found in eukaryotic cell membranes. In quiescent cells, the PtdIns(3,5)P2 levels, typically quantified by HPLC, are the lowest amongst the constitutively pr ...
, and PtdIns(3,4,5)P3) function in a mechanism by which an assorted group of signalling proteins, containing PX domains,
pleckstrin homology domain Pleckstrin homology domain (PH domain) or (PHIP) is a protein domain of approximately 120 amino acids that occurs in a wide range of proteins involved in intracellular signaling or as constituents of the cytoskeleton. This domain can bind phosp ...
s (PH domains),
FYVE domains In molecular biology the FYVE zinc finger domain is named after the four cysteine-rich proteins: Fab 1 (yeast orthologue of PIKfyve), YOTB, Vac 1 (vesicle transport protein), and EEA1, in which it has been found. FYVE domains bind phosphatidylin ...
or other phosphoinositide-binding domains, are recruited to various cellular membranes.


Function

PI3Ks have been linked to an extraordinarily diverse group of cellular functions, including cell growth, proliferation, differentiation, motility, survival and intracellular trafficking. Many of these functions relate to the ability of class I PI3Ks to activate
protein kinase B Protein kinase B (PKB), also known as Akt, is the collective name of a set of three serine/threonine-specific protein kinases that play key roles in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, t ...
(PKB, aka Akt) as in the
PI3K/AKT/mTOR pathway The PI3K/AKT/mTOR pathway is an intracellular signaling pathway important in regulating the cell cycle. Therefore, it is directly related to cellular quiescence, proliferation, cancer, and longevity. PI3K activation phosphorylates and activates ...
. The p110δ and
p110γ Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform is an enzyme that in humans is encoded by the ''PIK3CG'' gene. Function This gene encodes a protein that belongs to the pi3/pi4-kinase family of proteins. The gene p ...
isoforms regulate different aspects of immune responses. PI3Ks are also a key component of the
insulin signaling pathway Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
. Hence there is great interest in the role of PI3K signaling in
diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
. PI3K is also involved in interleukin signalling (IL4)


Mechanism

The
pleckstrin homology domain Pleckstrin homology domain (PH domain) or (PHIP) is a protein domain of approximately 120 amino acids that occurs in a wide range of proteins involved in intracellular signaling or as constituents of the cytoskeleton. This domain can bind phosp ...
of AKT binds directly to PtdIns(3,4,5)P3 and
PtdIns(3,4)P2 Phosphatidylinositol (3,4)-bisphosphate (PtdIns(3,4)''P''2) is a minor phospholipid component of cell membranes, yet an important second messenger. The generation of PtdIns(3,4)''P''2 at the plasma membrane activates a number of important cell sig ...
, which are produced by activated PI3Ks. Since PtdIns(3,4,5)P3 and PtdIns(3,4)P2 are restricted to the plasma membrane, this results in translocation of AKT to the plasma membrane. Likewise, the phosphoinositide-dependent kinase-1 (PDK1 or, rarely referred to as PDPK1) also contains a pleckstrin homology domain that binds directly to PtdIns(3,4,5)P3 and PtdIns(3,4)P2, causing it to also translocate to the plasma membrane upon PI3K activation. The interaction of activated PDK1 and AKT allows AKT to become phosphorylated by PDK1 on threonine 308, leading to partial activation of AKT. Full activation of AKT occurs upon phosphorylation of serine 473 by the TORC2 complex of the mTOR protein kinase. The
PI3K/AKT pathway The PI3K/AKT/mTOR pathway is an intracellular signaling pathway important in regulating the cell cycle. Therefore, it is directly related to cellular quiescence, proliferation, cancer, and longevity. PI3K activation phosphorylates and activates A ...
has been shown to be required for an extremely diverse array of cellular activities - most notably cellular proliferation and survival. For example, it was shown to be involved in the protection of astrocytes from ceramide-induced apoptosis. Many other proteins have been identified that are regulated by PtdIns(3,4,5)P3, including
Bruton's tyrosine kinase Bruton's tyrosine kinase (abbreviated Btk or BTK), also known as tyrosine-protein kinase BTK, is a tyrosine kinase that is encoded by the ''BTK'' gene in humans. BTK plays a crucial role in B cell development. Structure BTK contains five differ ...
(BTK), General Receptor for Phosphoinositides-1 (GRP1), and the O-linked N-acetylglucosamine (O-GlcNAc) transferase. PtdIns(3,4,5)P3 also activates guanine‐nucleotide exchange factors (GEFs) that activate the GTPase Rac1, leading to
actin Actin is a protein family, family of Globular protein, globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in myofibril, muscle fibrils. It is found in essentially all Eukaryote, eukaryotic cel ...
polymerization and cytoskeletal rearrangement.


Cancers

The class IA PI3K
p110α The phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (the HUGO-approved official symbol = PIK3CA; HGNC ID, HGNC:8975), also called p110α protein, is a class I PI 3-kinase catalytic subunit. The human p110α protein is enco ...
is mutated in many cancers. Many of these mutations cause the kinase to be more active. It is the single most mutated kinase in
glioblastoma Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality cha ...
, the most malignant primary brain tumor. The PtdIns(3,4,5)''P''3 phosphatase PTEN that antagonises PI3K signaling is absent from many tumours. In addition, the epidermal growth factor receptor EGFR that functions upstream of PI3K is mutationally activated or overexpressed in cancer. Hence, PI3K activity contributes significantly to cellular transformation and the development of
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...
. It has been shown that malignant B cells maintain a "tonic" activity of PI3K/Akt axis via upregulation of an adaptor protein GAB1, and this also allows B cells to survive targeted therapy with BCR inhibitors.


Learning and memory

PI3Ks have also been implicated in
long-term potentiation In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neurons ...
(LTP). Whether they are required for the expression or the induction of LTP is still debated. In mouse hippocampal CA1 neurons, certain PI3Ks are complexed with
AMPA receptor The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic transmembrane receptor for glutamate (iGluR) that mediates fast synaptic transmission in the ce ...
s and compartmentalized at the postsynaptic density of glutamatergic synapses. PI3Ks are phosphorylated upon
NMDA receptor The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA rece ...
-dependent CaMKII activity, and it then facilitates the insertion of AMPA-R GluR1 subunits into the plasma membrane. This suggests that PI3Ks are required for the expression of LTP. Furthermore, PI3K inhibitors abolished the expression of LTP in rat hippocampal CA1, but do not affect its induction. Notably, the dependence of late-phase LTP expression on PI3Ks seems to decrease over time. However, another study found that PI3K inhibitors suppressed the induction, but not the expression, of LTP in mouse hippocampal CA1. The
PI3K pathway Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which i ...
also recruits many other proteins downstream, including mTOR, GSK3β, and PSD-95. The PI3K-mTOR pathway leads to the phosphorylation of
p70S6K Ribosomal protein S6 kinase beta-1 (S6K1), also known as p70S6 kinase (p70S6K, p70-S6K), is an enzyme (specifically, a protein kinase) that in humans is encoded by the ''RPS6KB1'' gene. It is a serine/threonine kinase that acts downstream of PIP3 ...
, a kinase that facilitates translational activity, further suggesting that PI3Ks are required for the protein-synthesis phase of LTP induction instead. PI3Ks interact with the insulin receptor substrate (IRS) to regulate glucose uptake through a series of phosphorylation events.


PI 3-kinases as protein kinases

Many PI3Ks appear to have a serine/threonine kinase activity ''in vitro''; however, it is unclear whether this has any role ''in vivo''.


Inhibition

All PI3Ks are inhibited by the drugs
wortmannin Wortmannin, a steroid metabolite of the fungi '' Penicillium funiculosum'', ''Talaromyces wortmannii'', is a non-specific, covalent inhibitor of phosphoinositide 3-kinases (PI3Ks). It has an ''in vitro'' inhibitory concentration (''IC''50) of a ...
and
LY294002 LY294002 is a morpholine-containing chemical compound that is a potent inhibitor of numerous proteins, and a strong inhibitor of phosphoinositide 3-kinases (PI3Ks). It is generally considered a non-selective research tool, and should not be used f ...
, although certain members of the class II PI3K family show decreased sensitivity.
Wortmannin Wortmannin, a steroid metabolite of the fungi '' Penicillium funiculosum'', ''Talaromyces wortmannii'', is a non-specific, covalent inhibitor of phosphoinositide 3-kinases (PI3Ks). It has an ''in vitro'' inhibitory concentration (''IC''50) of a ...
shows better efficiency than
LY294002 LY294002 is a morpholine-containing chemical compound that is a potent inhibitor of numerous proteins, and a strong inhibitor of phosphoinositide 3-kinases (PI3Ks). It is generally considered a non-selective research tool, and should not be used f ...
on the hotspot mutation positions (GLU542, GLU545, and HIS1047)


PI3K inhibitors as therapeutics

As
wortmannin Wortmannin, a steroid metabolite of the fungi '' Penicillium funiculosum'', ''Talaromyces wortmannii'', is a non-specific, covalent inhibitor of phosphoinositide 3-kinases (PI3Ks). It has an ''in vitro'' inhibitory concentration (''IC''50) of a ...
and
LY294002 LY294002 is a morpholine-containing chemical compound that is a potent inhibitor of numerous proteins, and a strong inhibitor of phosphoinositide 3-kinases (PI3Ks). It is generally considered a non-selective research tool, and should not be used f ...
are broad-range inhibitors of PI3Ks and a number of unrelated proteins at higher concentrations, they are too toxic to be used as therapeutics. A number of pharmaceutical companies have thus developed PI3K isoform-specific inhibitors. As of January 2019, three PI3K inhibitors are approved by the FDA for routine clinical use in humans: the PIK3CD inhibitor idelalisib (July 2014
NDA 206545
, the dual PIK3CA and PIK3CD inhibitor copanlisib (September 2017
NDA 209936
, and the dual PIK3CD and PIK3CG inhibitor duvelisib (September 2018
NDA 211155
. Co-targeted inhibition of the pathway with other pathways such as MAPK or PIM has been highlighted as a promising anti-cancer therapeutic strategy, which could offer benefit over the monotherapeutic approach by circumventing compensatory signalling, slowing the development of resistance and potentially allowing reduction of dosing.


See also

*
PI3K/AKT/mTOR pathway The PI3K/AKT/mTOR pathway is an intracellular signaling pathway important in regulating the cell cycle. Therefore, it is directly related to cellular quiescence, proliferation, cancer, and longevity. PI3K activation phosphorylates and activates ...


References


Further reading

*

* * *


External links

* * to explore the structure in interactive 3D *
PI3K/Akt Signaling Pathway
{{DEFAULTSORT:Phosphoinositide 3-Kinase EC 2.7.1 Oncology