Extracellular signal-regulated kinases
Encyclopedia
In molecular biology
, extracellular-signal-regulated kinases (ERKs) or classical MAP kinases are widely expressed protein kinase
intracellular signalling molecules that are involved in functions including the regulation of meiosis
, mitosis
, and postmitotic functions in differentiated cells. Many different stimuli, including growth factors, cytokines, virus
infection, ligands for heterotrimeric G protein-coupled receptors, transforming agents, and carcinogens, activate the ERK pathway.
The term, "extracellular-signal-regulated kinases", is sometimes used as a synonym for mitogen-activated protein kinase
(MAPK), but has more recently been adopted for a specific subset of the mammal
ian MAPK family. In the MAPK/ERK pathway
, Ras activates c-Raf
, followed by mitogen-activated protein kinase kinase (abbreviated as MKK, MEK, or MAP2K) and then MAPK1/2 (below). Ras is typically activated by growth hormones through receptor tyrosine kinases and GRB2/SOS
, but may also receive other signals. ERKs are known to activate many transcription factors, such as ELK1
, and some downstream protein kinases. Disruption of the ERK pathway is common in cancers, especially Ras, c-Raf and receptors such as HER2.
is also known as "extracellular signal-regulated kinase 2" (ERK2). Two similar (85% sequence identity) protein kinases were originally called ERK1 and ERK2. They were found during a search for protein kinases that are rapidly phosphorylated after activation of cell surface tyrosine kinase
s such as the epidermal growth factor receptor
. Phosphorylation of ERKs leads to the activation of their kinase activity.
The molecular events linking cell surface receptors to activation of ERKs are complex. It was found that Ras GTP-binding proteins are involved in the activation of ERKs. Another protein kinase, Raf-1
, was shown to phosphorylate a "MAPK kinase", thus qualifying as a "MAPK kinase kinase". The MAPK kinase was named "MAPK/ERK kinase" (MEK).
Receptor-linked tyrosine kinases, Ras
, Raf, MEK
, and MAPK could be fitted into a signaling cascade linking an extracellular signal to MAPK activation. See: MAPK/ERK pathway
.
Transgenic gene knockout
mice lacking MAPK1 have major defects in early development.
is also known as "extracellular signal-regulated kinase 1" (ERK1). Transgenic gene knockout
mice lacking MAPK3
are viable and it is thought that MAPK1 can fulfill most MAPK3
functions in most cells. The main exception is in T cell
s. Mice lacking MAPK3
have reduced T cell development past the CD4+CD8+ stage.
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...
, extracellular-signal-regulated kinases (ERKs) or classical MAP kinases are widely expressed 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...
intracellular signalling molecules that are involved in functions including the regulation of meiosis
Meiosis
Meiosis is a special type of cell division necessary for sexual reproduction. The cells produced by meiosis are gametes or spores. The animals' gametes are called sperm and egg cells....
, mitosis
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...
, and postmitotic functions in differentiated cells. Many different stimuli, including growth factors, cytokines, virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
infection, ligands for heterotrimeric G protein-coupled receptors, transforming agents, and carcinogens, activate the ERK pathway.
The term, "extracellular-signal-regulated kinases", is sometimes used as a synonym for mitogen-activated protein kinase
Mitogen-activated protein kinase
Mitogen-activated protein kinases are serine/threonine-specific protein kinases that respond to extracellular stimuli and regulate various cellular activities, such as gene expression, mitosis, differentiation, proliferation, and cell survival/apoptosis.-Activation:MAP kinases are activated...
(MAPK), but has more recently been adopted for a specific subset of the mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
ian MAPK family. In the MAPK/ERK pathway
MAPK/ERK pathway
The MAPK/ERK pathway is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell. The signal starts when a growth factor binds to the receptor on the cell surface and ends when the DNA in the nucleus expresses a...
, Ras activates 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...
, followed by mitogen-activated protein kinase kinase (abbreviated as MKK, MEK, or MAP2K) and then MAPK1/2 (below). Ras is typically activated by growth hormones through receptor tyrosine kinases and GRB2/SOS
Son of Sevenless
In cell signalling, Son of Sevenless refers to a set of genes encoding guanine nucleotide exchange factors that act on the Ras subfamily of small GTPases.-History and name:...
, but may also receive other signals. ERKs are known to activate many transcription factors, such as ELK1
ELK1
E twenty-six -like transcription factor 1, also known as Elk1, functions as a transcription activator. It is classified as a ternary complex factor , a subclass of the ETS family, which is characterized by a common protein domain that regulates DNA binding to target sequences...
, and some downstream protein kinases. Disruption of the ERK pathway is common in cancers, especially Ras, c-Raf and receptors such as HER2.
Mitogen-activated protein kinase 1
Mitogen-activated protein kinase 1 (MAPK1)MAPK1
Mitogen-activated protein kinase 1, also known as MAPK1, p42MAPK, and ERK2, is an enzyme that in humans is encoded by the MAPK1 gene.- Function :The protein encoded by this gene is a member of the MAP kinase family...
is also known as "extracellular signal-regulated kinase 2" (ERK2). Two similar (85% sequence identity) protein kinases were originally called ERK1 and ERK2. They were found during a search for protein kinases that are rapidly phosphorylated after activation of cell surface tyrosine kinase
Tyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions....
s such as the epidermal growth factor receptor
Epidermal growth factor receptor
The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...
. Phosphorylation of ERKs leads to the activation of their kinase activity.
The molecular events linking cell surface receptors to activation of ERKs are complex. It was found that Ras GTP-binding proteins are involved in the activation of ERKs. Another protein kinase, Raf-1
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...
, was shown to phosphorylate a "MAPK kinase", thus qualifying as a "MAPK kinase kinase". The MAPK kinase was named "MAPK/ERK kinase" (MEK).
Receptor-linked tyrosine kinases, Ras
Ras
Ras is the name given to a family of related proteins found inside cells, including human cells. All Ras protein family members belong to a class of protein called small GTPase, and are involved in transmitting signals within cells...
, Raf, MEK
MEK
MEK or Mek may refer to:* In chemistry and industry methyl ethyl ketone, a solvent, used also to weld some plastics* The Iranian guerilla-cum-opposition group Mujahideen-e Khalq* Mek, a comic mini series by Warren Ellis...
, and MAPK could be fitted into a signaling cascade linking an extracellular signal to MAPK activation. See: MAPK/ERK pathway
MAPK/ERK pathway
The MAPK/ERK pathway is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell. The signal starts when a growth factor binds to the receptor on the cell surface and ends when the DNA in the nucleus expresses a...
.
Transgenic gene knockout
Gene knockout
A gene knockout is a genetic technique in which one of an organism's genes is made inoperative . Also known as knockout organisms or simply knockouts, they are used in learning about a gene that has been sequenced, but which has an unknown or incompletely known function...
mice lacking MAPK1 have major defects in early development.
Mitogen-activated protein kinase 3
Mitogen-activated protein kinase 3 (MAPK3)MAPK3
Mitogen-activated protein kinase 3 is an enzyme that in humans is encoded by the MAPK3 gene.-Interactions:MAPK3 has been shown to interact with PTPN7, SPIB, GTF2I, DUSP3, HDAC4, RPS6KA2, MAP2K1, DUSP6 and MAP2K2.-Further reading:...
is also known as "extracellular signal-regulated kinase 1" (ERK1). Transgenic gene knockout
Gene knockout
A gene knockout is a genetic technique in which one of an organism's genes is made inoperative . Also known as knockout organisms or simply knockouts, they are used in learning about a gene that has been sequenced, but which has an unknown or incompletely known function...
mice lacking MAPK3
MAPK3
Mitogen-activated protein kinase 3 is an enzyme that in humans is encoded by the MAPK3 gene.-Interactions:MAPK3 has been shown to interact with PTPN7, SPIB, GTF2I, DUSP3, HDAC4, RPS6KA2, MAP2K1, DUSP6 and MAP2K2.-Further reading:...
are viable and it is thought that MAPK1 can fulfill most MAPK3
MAPK3
Mitogen-activated protein kinase 3 is an enzyme that in humans is encoded by the MAPK3 gene.-Interactions:MAPK3 has been shown to interact with PTPN7, SPIB, GTF2I, DUSP3, HDAC4, RPS6KA2, MAP2K1, DUSP6 and MAP2K2.-Further reading:...
functions in most cells. The main exception is in T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s. Mice lacking MAPK3
MAPK3
Mitogen-activated protein kinase 3 is an enzyme that in humans is encoded by the MAPK3 gene.-Interactions:MAPK3 has been shown to interact with PTPN7, SPIB, GTF2I, DUSP3, HDAC4, RPS6KA2, MAP2K1, DUSP6 and MAP2K2.-Further reading:...
have reduced T cell development past the CD4+CD8+ stage.
External links
- The Extracellular Signal-Regulated Kinases
- MAP Kinase Resource .
- MAPK1
- MAPK3 Info with links in the Cell Migration Gateway