Mitogen-activated protein kinase 15, also known as MAPK15, ERK7, or ERK8, is an enzyme that in humans is encoded by the MAPK15 gene. [5] [6]
Evolutionarily, MAPK15 is conserved in a number of species, including P. troglodytes , B. taurus , M. musculus , R. norvegicus , D. rerio , D. melanogaster , C. elegans , and X. laevis . [6]
The protein encoded by this gene is a member of the MAP (mitogen-activated protein) kinase family. MAP kinases are also known as extracellular signal-regulated kinases (ERKs), and are involved in signaling cascades that regulate a number of cellular processes, including proliferation, differentiation, and transcriptional regulation. MAPK15 is often referred to as ERK7 or ERK8, and the latter two share 69% amino acid sequence similarity; at least one study has suggested that the two are, in fact, distinct proteins.
In vertebrate models, ERK8 is not constitutively active, and exhibits relatively low basal kinase activity. [7] It contains two SH3 (SRC homology 3) binding motifs in its C-terminal region, and is likely activated by an SRC-dependent signaling pathway. [5] SRC is a non-receptor tyrosine kinase (and proto-oncogene) that has been implicated in cancer growth and progression in humans when it is overexpressed. The exact function of MAPK15 is unknown, though a number of studies have implicated the enzyme in various cellular pathways.
Specifically, MAPK15 expression is significantly reduced in human lung and breast carcinomas, and MAPK15 down-regulation is correlated with increased cell motility. [7] MAPK15 has also been found to negatively regulate protein O-glycosylation with acetyl galactosamine (GalNAc), a process in which a sugar molecule is covalently attached to an oxygen atom on an amino acid residue. [7] Mammalian MAPK15 is a putative regulator of the cellular localization and transcriptional activity of estrogen-related receptor alpha (ERRa), as well as an inhibitor of proliferating cell nuclear antigen (PCNA) degradation. [8] [9] PCNA is critical for DNA replication, and is an essential factor in protecting genome stability. MAPK15 has also been shown to regulate ciliogenesis in X. laevis (African clawed frog) embryos by phosphorylating an actin regulator called CapZIP. [10]
MAPK15 has been demonstrated to interact with gamma-aminobutyric acid receptor-associated protein (GABARAP) and microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A, or LC3) in a process that stimulates autophagy. [11] A number of additional proteins also interact with MAPK15, including cyclin-dependent kinase 2 (CDK2), mitogen-activated protein kinase 12 (MAPK12), and lactotransferrin (LTF), among many others. [6]
Due to its role in protecting genomic integrity and cell motility, MAPK15 has been identified as a potential target for cancer therapeutics. [12] Additionally, given the putative role that MAPK15 plays in the regulation of ciliogenesis, it may be an ideal target for diseases related to human ciliary defects (often called ciliopathies).
Growth factor receptor-bound protein 2, also known as Grb2, is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene.
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 14, also called p38-α, is an enzyme that in humans is encoded by the MAPK14 gene.
Dual-specificity mitogen-activated protein kinase kinase 4 is an enzyme that in humans is encoded by the MAP2K4 gene.
MAP kinase-activated protein kinase 2 is an enzyme that in humans is encoded by the MAPKAPK2 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 protein phosphatase 1 is an enzyme that in humans is encoded by the DUSP1 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.
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.
protein S6 kinase, 90kDa, polypeptide 3, also s RPS6KA3, is an enzyme that in humans is encoded by the RPS6KA3 gene.
Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) is a signal transduction enzyme that in humans is encoded by the autosomal MAP3K1 gene.
General transcription factor II-I is a protein that in humans is encoded by the GTF2I 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.
G protein-coupled receptor kinase 5 is a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinases, and is most highly similar to GRK4 and GRK6. The protein phosphorylates the activated forms of G protein-coupled receptors to regulate their signaling.
Dual specificity mitogen-activated protein kinase kinase 5 is an enzyme that in humans is encoded by the MAP2K5 gene.
Mitogen-Activated Protein Kinase Kinase Kinase 2 also known as MEKK2 is an enzyme that in humans is encoded by the MAP3K2 gene.
Mitogen-activated protein kinase 6 is an enzyme that in humans is encoded by the MAPK6 gene.
Dual specificity protein phosphatase 4 is an enzyme that in humans is encoded by the DUSP4 gene.
Mitogen-activated protein kinase kinase kinase kinase 2 is an enzyme that in humans is encoded by the MAP4K2 gene.
