elk1

E twenty-six (ETS)-like transcription factor 1, also known as Elk1 or Member of ETS oncogene family (ELK1), is a member of the ETS oncogene superfamily which is characterized by a common protein domain that regulates DNA binding to target sequences. Elk1 is expressed in the nuclei of non-neuronal cells and function as a transcription activator. It plays important roles in various contexts, including long-term memory formation, drug addiction, Alzheimer's disease, Down syndrome, breast cancer, and depression.

Cytoplasmic Protein NCK1 (NCK1) is a cytoplasmic protein that contains one SH2 domain and three SH3 domains. NCK1 is a member of the adapter family, which associates with tyrosine-phosphorylated growth factor receptors, such as KDR and PDGFRB, or their cellular substrates. NCK1 maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. NCK1 plays a role in the DNA damage response, but not in the detection of the damage by ATM ATR. It is also involved in transducing signals from receptor tyrosine kinases to downstream signal recipients, such as ELK1-dependent transcriptional activation in response to activated Ras signaling.

E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. Involved in the TLR and IL-1 signaling pathways via interaction with the complex containing IRAK kinases and TRAF6. Mediates 'Lys-63'-linked polyubiquitination of IRAK1. Can activate AP1 JUN and ELK1. Not required for NF-kappa-B activation. PELI3 Protein, Human, Recombinant (His) is expressed in E. coli expression system with N-6xHis tag. The predicted molecular weight is 54.8 kDa and the accession number is Q8N2H9.

Coiled-coil domain containing 134 (CCDC134) is a 229 amino acids secretory protein. Coiled-coil domain is a motif in which alpha-helix are coiled together. It has been found in many types of proteins, including transcription factors, intermediate filaments and certain tRNA synthetases. Many proteins containing such motif CCDC134 are involved in important biological functions. CCDC134 is also considered as a novel human MAPK-regulating protein that can inhibit the MAPK pathway. This protein significantly inhibite Elk1 transcriptional activity. The coiled-coil domain is a ubiquitous protein motif that is often involved in oligomerization.

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 EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, 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.

MAPK14 contains 1 protein kinase domain and belongs to the MAP kinase family. MAP kinases 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. MAPK14 can be detected in the brain, heart, placenta, pancreas, and skeletal muscle and it is expressed to a lesser extent in the lung, liver, and kidney. MAPK14 is activated by various environmental stresses and proinflammatory cytokines. The activation requires its phosphorylation by MAP kinase kinases (MKKs), or its autophosphorylation triggered by the interaction of MAP3K7IP1 TAB1 protein with MAPK14. The substrates of p38 alpha include transcription regulator ATF2, MEF2C, and MAX, cell cycle regulator CDC25B, and tumor suppressor p53, which suggest the roles of p38 alpha in stress-related transcription and cell cycle regulation, as well as in genotoxic stress response. In response to activation by environmental stress, pro-inflammatory cytokines, and lipopolysaccharide, MAPK14 phosphorylates some transcription factors, such as ELK1 and ATF2, and several downstream kinases, such as MAPKAPK2 and MAPKAPK5. MAPK14 plays a critical role in the production of some cytokines, for example, IL-6. It may play a role in the stabilization of EPO mRNA during hypoxic stress. Isoform Mxi2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2.

Transcription factor that either stimulates or represses gene transcription through binding of different DNA regulatory elements such as cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), ATF5-specific response element (ARE) (consensus: 5'-C[CT]TCT[CT]CCTT[AT]-3') but also the amino acid response element (AARE), present in many viral and cellular promoters. Critically involved, often in a cell type-dependent manner, in cell survival, proliferation, and differentiation. Its transcriptional activity is enhanced by CCND3 and slightly inhibited by CDK4. Important regulator of the cerebral cortex formation, functions in cerebral cortical neuroprogenitor cells to maintain proliferation and to block differentiation into neurons. Must be down-regulated in order for such cells to exit the cycle and differentiate. Participates in the pathways by which SHH promotes cerebellar granule neuron progenitor cells proliferation. Critical for survival of mature olfactory sensory neurons (OSN), directs expression of OSN-specific genes. May be involved in osteogenic differentiation. Promotes cell proliferation and survival by inducing the expression of EGR1 sinergistically with ELK1. Once acetylated by EP300, binds to ARE sequences on target genes promoters, such as BCL2 and EGR1. Plays an anti-apoptotic role through the transcriptional regulation of BCL2, this function seems to be cell type-dependent. Cooperates with NR1I3 CAR in the transcriptional activation of CYP2B6 in liver. In hepatic cells, represses CRE-dependent transcription and inhibits proliferation by blocking at G2 M phase. May act as a negative regulator of IL1B transduction pathway in liver. Upon IL1B stimulus, cooperates with NLK to activate the transactivation activity of C EBP subfamily members. Besides its function of transcription factor, acts as a cofactor of CEBPB to activate CEBPA and promote adipocyte differentiation. Regulates centrosome dynamics in a cell-cycle- and centriole-age-dependent manner. Forms 9-foci symmetrical ring scaffold around the mother centriole to control centrosome function and the interaction between centrioles and pericentriolar material.