Mapk1
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.
Post-translational modifications
Dually phosphorylated on Thr-183 and Tyr-185, which activates the enzyme. Ligand-activated ALK induces tyrosine phosphorylation (By similarity). Dephosphorylated by PTPRJ at Tyr-185 (By similarity). Phosphorylated upon FLT3 and KIT signaling (By similarity). Dephosphorylated by DUSP1 and DUSP2 at Thr-183 and Tyr-185 (By similarity) (PubMed:8221888).
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.
Tissue Specificity
Widely expressed.
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-244 and Ser-246 as well as autophosphorylation at Thr-188 promote nuclear localization (By similarity). Localization to focal adhesions is stimulated by EGF (PubMed:15923189).
Alternative names
Erk2, Mapk, Prkm1, 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