Mouse Anti-MAPK1 (AA 154-183) Recombinant Antibody (814CT5.4.2) (CBMAB-E2138-FY)

Mitogen-Activated Protein Kinase 1

This gene encodes a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. The activation of this kinase requires its phosphorylation by upstream kinases. Upon activation, this kinase translocates to the nucleus of the stimulated cells, where it phosphorylates nuclear targets. One study also suggests that this protein acts as a transcriptional repressor independent of its kinase activity. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Two alternatively spliced transcript variants encoding the same protein, but differing in the UTRs, have been reported for this gene.

Mitogen-Activated Protein Kinase 1; Extracellular Signal-Regulated Kinase 2; Mitogen-Activated Protein Kinase 2; MAP Kinase Isoform P42; MAP Kinase 1; MAP Kinase 2; EC 2.7.11.24; P42-MAPK; MAPK 2; PRKM1; PRKM2; ERK-2; ERK2

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 plays also 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 EIAC F4EBP1) 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.

Apoptotic processManual Assertion Based On ExperimentTAS:ProtInc
B cell receptor signaling pathwayIEA:Ensembl
Bergmann glial cell differentiationIEA:Ensembl
Cardiac neural crest cell development involved in heart developmentIEA:Ensembl
Caveolin-mediated endocytosisManual Assertion Based On ExperimentTAS:UniProtKB
Cell cycleIEA:UniProtKB-KW
Cell surface receptor signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Cellular response to amino acid starvationManual Assertion Based On ExperimentIDA:CAFA
Cellular response to cadmium ionManual Assertion Based On ExperimentIMP:CAFA
Cellular response to DNA damage stimulusIEA:Ensembl
Cellular response to dopamineManual Assertion Based On ExperimentIMP:CAFA
Cellular response to granulocyte macrophage colony-stimulating factor stimulusIEA:Ensembl
Cellular response to reactive oxygen speciesManual Assertion Based On ExperimentIMP:CAFA
Cellular response to tumor necrosis factorIEA:Ensembl
Chemical synaptic transmissionManual Assertion Based On ExperimentTAS:ProtInc
ChemotaxisManual Assertion Based On ExperimentTAS:ProtInc
Cytosine metabolic processIEA:Ensembl
ERBB signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
ERK1 and ERK2 cascadeManual Assertion Based On ExperimentIDA:UniProtKB
Face developmentIEA:Ensembl
Iintracellular signal transductionManual Assertion Based On ExperimentIBA:GO_Central
Labyrinthine layer blood vessel developmentIEA:Ensembl
Learning or memory1 PublicationNAS:ARUK-UCL
Lipopolysaccharide-mediated signaling pathwayIEA:Ensembl
Long-term synaptic potentiationIEA:Ensembl
Lung morphogenesisIEA:Ensembl
Mammary gland epithelial cell proliferationIEA:Ensembl
Negative regulation of cell differentiationIEA:Ensembl
Outer ear morphogenesisIEA:Ensembl
Peptidyl-serine phosphorylationManual Assertion Based On ExperimentIDA:BHF-UCL
Peptidyl-threonine phosphorylationISS:UniProtKB
Positive regulation of gene expressionManual Assertion Based On ExperimentIMP:CAFA
Positive regulation of macrophage chemotaxisManual Assertion Based On ExperimentIGI:ARUK-UCL
Positive regulation of macrophage proliferationManual Assertion Based On ExperimentIGI:ARUK-UCL
Positive regulation of peptidyl-threonine phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of telomerase activityManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of telomere cappingManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of telomere maintenance via telomeraseManual Assertion Based On ExperimentIMP:BHF-UCL
Protein phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of cellular pHIEA:Ensembl
Regulation of cytoskeleton organizationManual Assertion Based On ExperimentTAS:UniProtKB
Regulation of early endosome to late endosome transportManual Assertion Based On ExperimentTAS:UniProtKB
Regulation of Golgi inheritanceManual Assertion Based On ExperimentTAS:UniProtKB
Regulation of ossificationIEA:Ensembl
Regulation of protein stabilityISS:UniProtKB
Regulation of stress-activated MAPK cascadeManual Assertion Based On ExperimentTAS:UniProtKB
Response to epidermal growth factorManual Assertion Based On ExperimentIDA:UniProtKB
Response to exogenous dsRNAIEA:Ensembl
Response to nicotineISS:ARUK-UCL
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc
Stress-activated MAPK cascadeManual Assertion Based On ExperimentIDA:CAFA
T cell receptor signaling pathwayIEA:Ensembl
Thymus developmentIEA:Ensembl
Thyroid gland developmentIEA:Ensembl
Trachea formationIEA:Ensembl

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

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.

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).