Dual specificity mitogen-activated protein kinase kinase 5 is an enzyme that in humans is encoded by the MAP2K5 gene. [5] [6]
Dual specificity mitogen-activated protein kinase kinase 5 is an enzyme that in humans is encoded by the MAP2K5 gene. [5] [6]
The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase specifically interacts with and activates MAPK7/ERK5. This kinase itself can be phosphorylated and activated by MAP3K3/MEKK3, as well as by atypical protein kinase C isoforms (aPKCs). The signal cascade mediated by this kinase is involved in growth factor stimulated cell proliferation and muscle cell differentiation. Four alternatively spliced transcript variants of this gene encoding distinct isoforms have been described. [6]
This kinase itself can be phosphorylated and activated by MAP3K3/MEKK3, as well as by atypical protein kinase C isoforms (aPKCs).
This kinase specifically interacts with and activates MAPK7/ERK5.
MAP2K5 has been shown to interact with MAPK7, [5] MAP3K2, [7] Protein kinase Mζ [8] and MAP3K3. [7] [9]
A mitogen-activated protein kinase is a type of protein kinase that is specific to the amino acids serine and threonine. MAPKs are involved in directing cellular responses to a diverse array of stimuli, such as mitogens, osmotic stress, heat shock and proinflammatory cytokines. They regulate cell functions including proliferation, gene expression, differentiation, mitosis, cell survival, and apoptosis.
Mitogen Activated Protein (MAP) kinase kinase kinase, MAPKKK is a serine/threonine-specific protein kinase which acts upon MAP kinase kinase. Subsequently, MAP kinase kinase activates MAP kinase. Several types of MAPKKK can exist but are mainly characterized by the MAP kinases they activate. MAPKKKs are stimulated by a large range of stimuli, primarily environmental and intracellular stressors. MAPKKK is responsible for various cell functions such as cell proliferation, cell differentiation, and apoptosis. The duration and intensity of signals determine which pathway ensues. Additionally, the use of protein scaffolds helps to place the MAPKKK in close proximity with its substrate to allow for a reaction. Lastly, because MAPKKK is involved in a series of several pathways, it has been used as a therapeutic target for cancer, amyloidosis, and neurodegenerative diseases. In humans, there are at least 19 genes which encode MAP kinase kinase kinases:
RAF kinases are a family of three serine/threonine-specific protein kinases that are related to retroviral oncogenes. The mouse sarcoma virus 3611 contains a RAF kinase-related oncogene that enhances fibrosarcoma induction. RAF is an acronym for Rapidly Accelerated Fibrosarcoma.
U0126 is a highly selective inhibitor of both MEK1 and MEK2, a type of MAPK/ERK kinase. U0126 was found to functionally antagonize AP-1 transcriptional activity via noncompetitive inhibition of the dual specificity kinase MEK with IC50 of 72 nM for MEK1 and 58 nM for MEK2. U0126 inhibited anchorage-independent growth of Ki-ras-transformed rat fibroblasts by simultaneously blocking both extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR)-p70(S6K) pathways. The effects of U0126 on the growth of eight human breast cancer cell lines shown that U0126 selectively repressed anchorage-independent growth of MDA-MB231 and HBC4 cells, two lines with constitutively activated ERK. Loss of contact with substratum triggers apoptosis in many normal cell types, a phenomenon termed anoikis. U0126 sensitized MDA-MB231 and HBC4 to anoikis, i.e., upon treatment with U0126, cells deprived of anchorage entered apoptosis.
Apoptosis signal-regulating kinase 1 (ASK1) also known as mitogen-activated protein kinase 5 (MAP3K5) is a member of MAP kinase family and as such a part of mitogen-activated protein kinase pathway. It activates c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases in a Raf-independent fashion in response to an array of stresses such as oxidative stress, endoplasmic reticulum stress and calcium influx. ASK1 has been found to be involved in cancer, diabetes, rheumatoid arthritis, cardiovascular and neurodegenerative diseases.
Mitogen-activated protein kinase 1, (MAPK 1), also known as ERK2, is an enzyme that in humans is encoded by the MAPK1 gene.
Mitogen-activated protein kinase 14, also called p38-α, is an enzyme that in humans is encoded by the MAPK14 gene.
Mitogen-activated protein kinase 3, also known as p44MAPK and ERK1, is an enzyme that in humans is encoded by the MAPK3 gene.
Dual specificity mitogen-activated protein kinase kinase 1 is an enzyme that in humans is encoded by the MAP2K1 gene.
Dual specificity mitogen-activated protein kinase kinase 2 is an enzyme that in humans is encoded by the MAP2K2 gene. It is more commonly known as MEK2, but has many alternative names including CFC4, MKK2, MAPKK2 and PRKMK2.
Dual-specificity mitogen-activated protein kinase kinase 4 is an enzyme that in humans is encoded by the MAP2K4 gene.
Mitogen-activated protein kinase 7 also known as MAP kinase 7 is an enzyme that in humans is encoded by the MAPK7 gene.
Dual specificity mitogen-activated protein kinase kinase 6 also known as MAP kinase kinase 6 or MAPK/ERK kinase 6 is an enzyme that in humans is encoded by the MAP2K6 gene, on chromosome 17.
Dual specificity mitogen-activated protein kinase kinase 3 is an enzyme that in humans is encoded by the MAP2K3 gene.
Mitogen-activated protein kinase kinase kinase 3 is an enzyme that in humans is encoded by the MAP3K3 gene, which is located on the long arm of chromosome 17 (17q23.3).
Ribosomal protein S6 kinase alpha-1 is an enzyme that in humans is encoded by the RPS6KA1 gene.
Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) is a signal transduction enzyme that in humans is encoded by the autosomal MAP3K1 gene.
Dual specificity mitogen-activated protein kinase kinase 7, also known as MAP kinase kinase 7 or MKK7, is an enzyme that in humans is encoded by the MAP2K7 gene. This protein is a member of the mitogen-activated protein kinase kinase family. The MKK7 protein exists as six different isoforms with three possible N-termini and two possible C-termini.
Mitogen-activated protein kinase kinase kinase 4 is an enzyme that in humans is encoded by the MAP3K4 gene.
Mitogen-Activated Protein Kinase Kinase Kinase 2 also known as MEKK2 is an enzyme that in humans is encoded by the MAP3K2 gene.
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