MAPK1

GeneName

MAPK1

Summary

MAPK1, also known as ERK2 or ERK-2, is a 41 kDa serine/threonine kinase that plays a pivotal role in various signalling pathways. It is predominantly expressed in the cytoplasm but can also be found in the nucleus, mitochondria, and at the plasma membrane. MAPK1 is integral to the MAPK cascade, which is essential for transmitting signals from the cell surface to the nucleus, thereby regulating processes such as cell proliferation, differentiation, and survival. It is involved in numerous biological processes including the apoptotic process, B cell receptor signalling, and responses to growth factors. The protein interacts with a variety of substrates through its kinase activity, influencing diverse cellular functions and pathways.

Importance

MAPK1 is relevant to: - Cancer research due to its role in cell proliferation and survival pathways, making it a target for therapeutic interventions. - Neurobiology as it is involved in learning and memory processes through its role in synaptic plasticity. - Cardiovascular development and function, impacting heart development and response to stress signals. - Immune responses, particularly in T cell receptor signalling and macrophage chemotaxis, influencing inflammation and immune system regulation.

Top Products

For researchers investigating MAPK1, we recommend two excellent primary antibodies. The first is the well-cited polyclonal antibody, Anti-ERK1 + ERK2 antibody (ab17942), which has garnered 428 citations, highlighting its reliability in Western blotting (WB), immunohistochemistry (IHC), and immunocytochemistry (ICC). Additionally, we offer the recombinant monoclonal antibody, Anti-ERK1 + ERK2 antibody [EPR17526] (ab184699). This product has been validated in knockout models and is suitable for a broader range of applications, including WB, ICC, flow cytometry (FC), and immunoprecipitation (IP). With 392 citations, it is also well-regarded in the research community, making it a versatile choice for those needing consistent and reliable detection of MAPK1. The Anti-ERK1 + ERK2 antibody ELISA Kit (ab54230), supported by 135 citations, is an excellent option for researchers looking to accurately measure MAPK1 levels in their samples.

Abcam Product Citation Summary

The data indicates that MAPK1 is frequently studied in various contexts, particularly in relation to cancer and cell signalling. The use of western blotting and immunohistochemistry highlights its importance in understanding the molecular mechanisms underlying diseases such as colon cancer and liver cancer. Additionally, studies involving mouse models suggest a significant role of MAPK1 in inflammatory responses and cellular growth.

Abcam Product Citation Table

Domain

The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.

Function

Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade also plays a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1 and FXR1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in response to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. Phosphorylates CDK2AP2 (By similarity).

Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity.

Involvement in disease

Noonan syndrome 13

NS13

A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. NS13 inheritance is autosomal dominant. There is considerable variability in severity.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Phosphorylated upon KIT and FLT3 signaling (By similarity). Dually phosphorylated on Thr-185 and Tyr-187, which activates the enzyme. Undergoes regulatory phosphorylation on additional residues such as Ser-246 and Ser-248 in the kinase insert domain (KID) These phosphorylations, which are probably mediated by more than one kinase, are important for binding of MAPK1/ERK2 to importin-7 (IPO7) and its nuclear translocation. In addition, autophosphorylation of Thr-190 was shown to affect the subcellular localization of MAPK1/ERK2 as well. Ligand-activated ALK induces tyrosine phosphorylation. Dephosphorylated by PTPRJ at Tyr-187. Phosphorylation on Ser-29 by SGK1 results in its activation by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. DUSP3 and DUSP6 dephosphorylate specifically MAPK1/ERK2 and MAPK3/ERK1 whereas DUSP9 dephosphorylates a broader range of MAPKs. Dephosphorylated by DUSP1 and DUSP2 at Thr-185 and Tyr-187 (By similarity) (PubMed:16288922).

ISGylated.

Ubiquitinated by TRIM15 via 'Lys-63'-linked ubiquitination; leading to activation. Deubiquitinated by CYLD.

Sequence Similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.

Cellular localization

• Cytoplasm
• Cytoskeleton
• Spindle
• Nucleus
• Cytoplasm
• Cytoskeleton
• Microtubule organizing center
• Centrosome
• Cytoplasm
• Membrane
• Caveola
• Cell junction
• Focal adhesion
• Associated with the spindle during prometaphase and metaphase (By similarity). PEA15-binding and phosphorylated DAPK1 promote its cytoplasmic retention. Phosphorylation at Ser- 246 and Ser-248 as well as autophosphorylation at Thr-190 promote nuclear localization.

Alternative names

ERK2, PRKM1, PRKM2, MAPK1, Mitogen-activated protein kinase 1, MAP kinase 1, MAPK 1, ERT1, Extracellular signal-regulated kinase 2, MAP kinase isoform p42, Mitogen-activated protein kinase 2, ERK-2, p42-MAPK, MAP kinase 2, MAPK 2

Database links

swissprot:P28482 omim:601795 omim:176948 swissprot:P27361 entrezGene:5594 entrezGene:5595