MAPK3

GeneName

MAPK3

Summary

MAPK3, also known as ERK1 or p44 MAPK, is a 43kDa serine/threonine kinase that plays a pivotal role in various cellular processes, including proliferation, differentiation, and apoptosis. It is primarily localised in the cytoplasm and nucleus, and is involved in the MAPK signalling pathway, which transmits signals from cell surface receptors to the nucleus. MAPK3 is activated by various stimuli, such as growth factors and stress signals, leading to its role in regulating gene expression through phosphorylation of transcription factors. It is also implicated in several biological processes, including the cellular response to mechanical stimulus, insulin receptor signalling, and modulation of synaptic transmission.

Importance

MAPK3 is relevant to: - Cancer research due to its involvement in cell proliferation and survival pathways, making it a potential target for therapeutic intervention. - Neurobiology, particularly in the context of synaptic plasticity and memory formation, as it regulates processes critical for learning and memory. - Cardiovascular development and function, given its role in cardiac neural crest cell development and response to growth factors. - Immune responses, as it modulates T cell activity and macrophage function, influencing inflammation and immune regulation.

Top Products

For researchers investigating MAPK3, we highly recommend the top-selling recombinant monoclonal antibody, Anti-ERK1 antibody [Y72] (ab32537). This antibody has been validated in knockout models, ensuring its reliability in various applications, including Western blotting (WB), immunohistochemistry (IHC), immunocytochemistry (ICC), flow cytometry (FC), and immunoprecipitation (IP). With 99 citations, it is well-regarded in the research community, making it an excellent choice for those seeking robust and consistent results in their studies of MAPK3.

Abcam Product Citation Summary

The data indicates a significant focus on MAPK3 in various human and animal models, particularly in studies related to cancer, diabetes, and cellular signaling pathways. The use of multiple antibodies across different species highlights the importance of MAPK3 in understanding disease mechanisms and therapeutic responses.

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 (PubMed:34497368). 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 a variety of other signaling-related molecules (like ARHGEF2, DEPTOR, FRS2 or GRB10) (PubMed:35216969). 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.

Post-translational modifications

Phosphorylated upon KIT and FLT3 signaling (By similarity). Dually phosphorylated on Thr-202 and Tyr-204, which activates the enzyme. Ligand-activated ALK induces tyrosine phosphorylation. Dephosphorylated by PTPRJ at Tyr-204.

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
• Nucleus
• Membrane
• Caveola
• Cell junction
• Focal adhesion
• Autophosphorylation at Thr-207 promotes nuclear localization (PubMed:19060905). PEA15-binding redirects the biological outcome of MAPK3 kinase-signaling by sequestering MAPK3 into the cytoplasm (By similarity).

Alternative names

ERK1, PRKM3, MAPK3, Mitogen-activated protein kinase 3, MAP kinase 3, MAPK 3, ERT2, Extracellular signal-regulated kinase 1, Insulin-stimulated MAP2 kinase, MAP kinase isoform p44, Microtubule-associated protein 2 kinase, p44-ERK1, ERK-1, p44-MAPK

Database links

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

Other research areas

• Immunology & Infectious Disease