Mitogen-activated protein kinase 1

Mitogen-activated protein kinase 1

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, GLI1 or GRB10)35831023. 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). Phosphorylates phosphoglycerate kinase PGK1 under hypoxic conditions to promote its targeting to the mitochondrion and suppress the formation of acetyl-coenzyme A from pyruvate26942675. Phosphorylates GJA1 at 'Ser-279' and 'Ser-282' resulting in an increase in GJA1 ubiquitination and ultimately lysosomal degradation (By similarity). Acts as a positive regulator of smoothened signaling by mediating phosphorylation of GLI1 in response to smoothened activation, promoting its dissociation from SUFU inhibitor and translocation to the nucleus35831023

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

Quoted from UniProt’s FUNCTION annotation for P28482 (reviewed). The superscript numbers are UniProt’s own PubMed citations, kept in the sentence and in order, each linking to the paper it names.

What it acts with

STRING’s highest-confidence human functional partners. The combined score mixes several kinds of evidence, so each channel is shown separately — a partner supported by experiment is a different claim from one supported only by text mining, and for a receptor this is where its coupling appears as evidence rather than as assertion.

Where it sits in the cell

• Nucleoplasm
• Microtubulesadditional
• Primary ciliumadditional
• Primary cilium tipadditional
• Basal bodyadditional
• Cytosoladditional

Human Protein Atlas, by antibody immunofluorescence in cell lines — a different assay from the expression figures below, which are RNA.

UniProt, curated Cytoplasm, cytoskeleton, spindle · Nucleus · Cytoplasm, cytoskeleton, microtubule organizing center, centrosome · Cytoplasm · Membrane, caveola · Cell junction, focal adhesion

Expression by cell type

Single cell type RNA, the 3 highest of those the Human Protein Atlas reports for this gene. Transcript, not protein, and a cell type rather than a tissue.

• Neutrophils1,044.8 nCPM
• Neutrophil progenitors707.3 nCPM
• Mast cells608.3 nCPM