Phosphatidylinositol-4,5-bisphosphate 3-kinase
Encyclopedia
In enzymology, a phosphatidylinositol-4,5-bisphosphate 3-kinase is an enzyme
that catalyzes
the chemical reaction
Thus, the two substrates
of this enzyme are ATP
and 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate, whereas its two products
are ADP
and 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate.
This enzyme belongs to the family of transferase
s, specifically those transferring phosphorus-containing groups (phosphotransferase
s) with an alcohol group as acceptor. The systematic name of this enzyme class is ATP:1-phosphatidyl-1D-myo-inositol-4,5-bisphosphate 3-phosphotransferase. This enzyme is also called type I phosphoinositide 3-kinase. This enzyme participates in 29 metabolic pathways
: inositol phosphate metabolism, erbb signaling pathway, phosphatidylinositol signaling system, mtor signaling pathway, apoptosis
, vegf signaling pathway, focal adhesion
, toll-like receptor signaling pathway, jak-stat signaling pathway
, natural killer cell mediated cytotoxicity, t cell receptor signaling pathway, b cell receptor signaling pathway, fc epsilon ri signaling pathway, leukocyte transendothelial migration, regulation of actin cytoskeleton, insulin signaling pathway, progesterone-mediated oocyte maturation, type ii diabetes mellitus, colorectal cancer
, renal cell carcinoma
, pancreatic cancer
, endometrial cancer
, glioma
, prostate cancer
, melanoma
, chronic myeloid leukemia, acute myeloid leukemia
, small cell lung cancer, and non-small cell lung cancer.
have been solved for this class of enzymes, with PDB
accession codes , , , , , and .
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 catalyzes
Catalysis
Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....
the chemical reaction
Chemical reaction
A chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, typically following the input of some type of energy, such as heat, light or electricity...
- ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
Thus, the two substrates
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
of this enzyme are ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
and 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate, whereas its two products
Product (chemistry)
Product are formed during chemical reactions as reagents are consumed. Products have lower energy than the reagents and are produced during the reaction according to the second law of thermodynamics. The released energy comes from changes in chemical bonds between atoms in reagent molecules and...
are ADP
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....
and 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate.
This enzyme belongs to the family of transferase
Transferase
In biochemistry, a transferase is an enzyme that catalyzes the transfer of a functional group from one molecule to another . For example, an enzyme that catalyzed this reaction would be a transferase:In this example, A would be the donor, and B would be the acceptor...
s, specifically those transferring phosphorus-containing groups (phosphotransferase
Phosphotransferase
Phosphotransferases are a category of enzymes that catalyze phosphorylation reactions. The general form of the reactions they catalyze is: A—P + B ⇔ B—P + A...
s) with an alcohol group as acceptor. The systematic name of this enzyme class is ATP:1-phosphatidyl-1D-myo-inositol-4,5-bisphosphate 3-phosphotransferase. This enzyme is also called type I phosphoinositide 3-kinase. This enzyme participates in 29 metabolic pathways
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
: inositol phosphate metabolism, erbb signaling pathway, phosphatidylinositol signaling system, mtor signaling pathway, 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...
, vegf signaling pathway, focal adhesion
Focal adhesion
In cell biology, focal adhesions are specific types of large macromolecular assemblies through which both mechanical force and regulatory signals are transmitted. More precisely, they can be considered as sub-cellular macromolecules that mediate the regulatory effects In cell biology, focal...
, toll-like receptor signaling pathway, jak-stat signaling pathway
JAK-STAT signaling pathway
The JAK-STAT signaling pathway transmits information from chemical signals outside the cell, through the cell membrane, and into gene promoters on the DNA in the cell nucleus, which causes DNA transcription and activity in the cell. The JAK-STAT system is a major signaling alternative to the second...
, natural killer cell mediated cytotoxicity, t cell receptor signaling pathway, b cell receptor signaling pathway, fc epsilon ri signaling pathway, leukocyte transendothelial migration, regulation of actin cytoskeleton, insulin signaling pathway, progesterone-mediated oocyte maturation, type ii diabetes mellitus, colorectal cancer
Colorectal cancer
Colorectal cancer, commonly known as bowel cancer, is a cancer caused by uncontrolled cell growth , in the colon, rectum, or vermiform appendix. Colorectal cancer is clinically distinct from anal cancer, which affects the anus....
, renal cell carcinoma
Renal cell carcinoma
Renal cell carcinoma is a kidney cancer that originates in the lining of the proximal convoluted tubule, the very small tubes in the kidney that filter the blood and remove waste products. RCC is the most common type of kidney cancer in adults, responsible for approximately 80% of cases...
, pancreatic cancer
Pancreatic cancer
Pancreatic cancer refers to a malignant neoplasm of the pancreas. The most common type of pancreatic cancer, accounting for 95% of these tumors is adenocarcinoma, which arises within the exocrine component of the pancreas. A minority arises from the islet cells and is classified as a...
, endometrial cancer
Endometrial cancer
Endometrial cancer refers to several types of malignancies that arise from the endometrium, or lining, of the uterus. Endometrial cancers are the most common gynecologic cancers in the United States, with over 35,000 women diagnosed each year. The incidence is on a slow rise secondary to the...
, glioma
Glioma
A glioma is a type of tumor that starts in the brain or spine. It is called a glioma because it arises from glial cells. The most common site of gliomas is the brain.-By type of cell:...
, prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
, melanoma
Melanoma
Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...
, chronic myeloid leukemia, acute myeloid leukemia
Acute myeloid leukemia
Acute myeloid leukemia , also known as acute myelogenous leukemia, is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute...
, small cell lung cancer, and non-small cell lung cancer.
Structural studies
As of late 2007, 6 structuresTertiary structure
In biochemistry and molecular biology, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates.-Relationship to primary structure:...
have been solved for this class of enzymes, with PDB
Protein Data Bank
The Protein Data Bank is a repository for the 3-D structural data of large biological molecules, such as proteins and nucleic acids....
accession codes , , , , , and .
Examples
Human genes encoding proteins with phosphatidylinositol-4,5-bisphosphate 3-kinase activity include:- PIK3CA
- PIK3CBPIK3CBPhosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta isoform is an enzyme that in humans is encoded by the PIK3CB gene.-Further reading:...
- PIK3CDP110δPhosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta isoform also known as phosphoinositide 3-kinase or p110δ is an enzyme that in humans is encoded by the PIK3CD gene....
- PIK3CGPIK3CGPhosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform is an enzyme that in humans is encoded by the PIK3CG gene.-Interactions:PIK3CG has been shown to interact with PIK3CD, KRAS, PIK3R5 and BCR gene.-Further reading:...