Search results for MAPK14

Showing 16 results out of 17

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Protein (6 results from a total of 7)

Identifier: R-HSA-446223
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: MAPK14: Q16539
Identifier: R-HSA-6803300
Species: Homo sapiens
Compartment: secretory granule lumen
Primary external reference: UniProt: MAPK14: Q16539
Identifier: R-HSA-6803280
Species: Homo sapiens
Compartment: ficolin-1-rich granule lumen
Primary external reference: UniProt: MAPK14: Q16539
Identifier: R-HSA-428933
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: Q16539
Identifier: R-HSA-6806453
Species: Homo sapiens
Compartment: extracellular region
Primary external reference: UniProt: Q16539
Identifier: R-HSA-428935
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: MAPK14: Q16539

Interactor (1 results from a total of 1)

Identifier: Q16539-3
Species: Homo sapiens
Primary external reference: UniProt: Q16539-3

Set (3 results from a total of 3)

Identifier: R-HSA-9662745
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-203795
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-198703
Species: Homo sapiens
Compartment: nucleoplasm

Reaction (4 results from a total of 4)

Identifier: R-HSA-9662823
Species: Homo sapiens
Compartment: cytosol, plasma membrane
The phosphorylation of disintegrin and metalloproteinase domain-containing protein 17 (ADAM17) by PLK2 and MAPKs has been determined by direct and indirect experiments (Müllberg et al. 1993, Schwarz et al. 2014, Fan and Derynck 1999; Gechtman et al. 1999; Díaz-Rodríguez et al. 2002; Fan, Turck, and Derynck 2003 & Xu and Derynck 2010). Specifically, the phosphorylation at residues Thr735 (Díaz-Rodríguez et al. 2002 & Xu and Derynck 2010) and Ser819 is required for ectodomains shedding.
Identifier: R-HSA-9626880
Species: Homo sapiens
Compartment: cytosol
In resting cells, the neutrophil cytosolic factor 1 (NCF1, also known as p47phox), NCF2 (p67phox), and NCF4 (p40phox) are located in the cytosol where they associate in a trimer complex with a 1:1:1 stoichiometry through specific domains (Groemping Y & Rittinger K 2005; El-Benna J et al. 2005; Park JW et al. 1994; Lapouge K et al. 2002; El-Benna J et al. 2016). However, NCF1 may also exist separately from the trimer (El-Benna J et al. 2016). In the resting state, two SH3 domains of NCF1 (p47phox) bind the auto‐inhibitory region (AIR; amino acids 292‐340) to keep NCF1 in a closed auto‐inhibited state, preventing its binding to p22phox and therefore NOX2 activation (Groemping Y et al. 2003; Yuzawa S et al. 2004; El-Benna J et al. 2016). Priming of neutrophils by several agents such as GM‐CSF, TNFα, PAF, LPS and CL097, a TLR7/8 agonist, induces partial phosphorylation of NCF1 (Makni-Maalej K et al. 2015; Dang PM et al. 1999; Dewas C et al. 2003; DeLeo FR et al. 1998). Mass spectrometry analysis of NCF1 identified Ser345 as the phosphorylated site in human neutrophils primed by TNFα and GM‐CSF (Dang PMC et al. 2006). Site‐directed mutagenesis of Ser345 and use of a competitive inhibitory peptide containing the Ser345 sequence have demonstrated that this step is critical for the priming of ROS production in human neutrophils (Dang PMC et al. 2006). Further, inhibitors of the p38 MAPK abrogated TNF-alpha- and TLR8 agonist-induced phosphorylation of Ser345 (Dang PMC et al. 2006; Makni-Maalej K et al. 2015).
Identifier: R-HSA-3238999
Species: Homo sapiens
Compartment: nucleoplasm
MAPKAPK5 (PRAK) forms a complex with MAPK14 (p38 alpha) or MAPK11 (p38 beta) irrespective of the phosphorylation status and kinase activity of MAPKAPK5, MAPK14 and MAPK11 (New et al. 2003). Phosphorylation of p38 alpha and p38 beta by MKK3 or MKK6 (Raingeaud et al. 1996), however, is required for the subsequent activation of MAPKAPK5 by p38 MAPK (New et al. 1998, Sun et al. 2007).
Identifier: R-HSA-3239019
Species: Homo sapiens
Compartment: nucleoplasm
MAPK14 (p38 alpha) and MAPK11 (p38 beta) phosphorylate MAPKAPK5 (PRAK) on threonine residue 182, located in the conserved LMTP site in the T-loop of the kinase domain. Phosphorylation of T182 is necessary for the MAPKAPK5 catalytic activity (New et al. 1998).

Pathway (2 results from a total of 2)

Identifier: R-HSA-446652
Species: Homo sapiens
Compartment: plasma membrane
The Interleukin-1 (IL1) family of cytokines comprises 11 members, namely Interleukin-1 alpha (IL1A), Interleukin-1 beta (IL1B), Interleukin-1 receptor antagonist protein (IL1RN, IL1RA), Interleukin-18 (IL18), Interleukin-33 (IL33), Interleukin-36 receptor antagonist protein (IL36RN, IL36RA), Interleukin-36 alpha (IL36A), Interleukin-36 beta (IL36B), Interleukin-36 gamma (IL36G), Interleukin-37 (IL37) and Interleukin-38 (IL38). The genes encoding all except IL18 and IL33 are on chromosome 2. They share a common C-terminal three-dimensional structure and with apart from IL1RN they are synthesized without a hydrophobic leader sequence and are not secreted via the classical reticulum endoplasmic-Golgi pathway. IL1B and IL18, are produced as biologically inactive propeptides that are cleaved to produce the mature, active interleukin peptide. The IL1 receptor (IL1R) family comprises 10 members: Interleukin-1 receptor type 1 (IL1R1, IL1RA), Interleukin-1 receptor type 2 (IL1R2, IL1RB), Interleukin-1 receptor accessory protein (IL1RAP, IL1RAcP, IL1R3), Interleukin-18 receptor 1 (IL18R1, IL18RA) , Interleukin-18 receptor accessory protein (IL18RAP, IL18RB), Interleukin-1 receptor-like 1 (IL1RL1, ST2, IL33R), Interleukin-1 receptor-like 2 (IL1RL2, IL36R), Single Ig IL-1-related receptor (SIGIRR, TIR8), Interleukin-1 receptor accessory protein-like 1 (IL1RAPL1, TIGGIR2) and X-linked interleukin-1 receptor accessory protein-like 2 (IL1RAPL2, TIGGIR1). Most of the genes encoding these receptors are on chromosome 2. IL1 family receptors heterodimerize upon cytokine binding. IL1, IL33 and IL36 bind specific receptors, IL1R1, IL1RL1, and IL1RL2 respectively. All use IL1RAP as a co-receptor. IL18 binds IL18R1 and uses IL18RAP as co-receptor. The complexes formed by IL1 family cytokines and their heterodimeric receptors recruit intracellular signaling molecules, including Myeloid differentiation primary response protein MyD88 (MYD88), members of he IL1R-associated kinase (IRAK) family, and TNF receptor-associated factor 6 (TRAF6), activating Nuclear factor NF-kappa-B (NFκB), as well as Mitogen-activated protein kinase 14 (MAPK14, p38), c-Jun N-terminal kinases (JNKs), extracellular signal-regulated kinases (ERKs) and other Mitogen-activated protein kinases (MAPKs).
Identifier: R-HSA-2559580
Species: Homo sapiens
Oxidative stress, caused by increased concentration of reactive oxygen species (ROS) in the cell, can happen as a consequence of mitochondrial dysfunction induced by the oncogenic RAS (Moiseeva et al. 2009) or independent of oncogenic signaling. Prolonged exposure to interferon-beta (IFNB, IFN-beta) also results in ROS increase (Moiseeva et al. 2006). ROS oxidize thioredoxin (TXN), which causes TXN to dissociate from the N-terminus of MAP3K5 (ASK1), enabling MAP3K5 to become catalytically active (Saitoh et al. 1998). ROS also stimulate expression of Ste20 family kinases MINK1 (MINK) and TNIK through an unknown mechanism, and MINK1 and TNIK positively regulate MAP3K5 activation (Nicke et al. 2005).


MAP3K5 phosphorylates and activates MAP2K3 (MKK3) and MAP2K6 (MKK6) (Ichijo et al. 1997, Takekawa et al. 2005), which act as p38 MAPK kinases, as well as MAP2K4 (SEK1) (Ichijo et al. 1997, Matsuura et al. 2002), which, together with MAP2K7 (MKK7), acts as a JNK kinase.


MKK3 and MKK6 phosphorylate and activate p38 MAPK alpha (MAPK14) and beta (MAPK11) (Raingeaud et al. 1996), enabling p38 MAPKs to phosphorylate and activate MAPKAPK2 (MK2) and MAPKAPK3 (MK3) (Ben-Levy et al. 1995, Clifton et al. 1996, McLaughlin et al. 1996, Sithanandam et al. 1996, Meng et al. 2002, Lukas et al. 2004, White et al. 2007), as well as MAPKAPK5 (PRAK) (New et al. 1998 and 2003, Sun et al. 2007).


Phosphorylation of JNKs (MAPK8, MAPK9 and MAPK10) by MAP3K5-activated MAP2K4 (Deacon and Blank 1997, Fleming et al. 2000) allows JNKs to migrate to the nucleus (Mizukami et al. 1997) where they phosphorylate JUN. Phosphorylated JUN binds FOS phosphorylated by ERK1 or ERK2, downstream of activated RAS (Okazaki and Sagata 1995, Murphy et al. 2002), forming the activated protein 1 (AP-1) complex (FOS:JUN heterodimer) (Glover and Harrison 1995, Ainbinder et al. 1997).


Activation of p38 MAPKs and JNKs downstream of MAP3K5 (ASK1) ultimately converges on transcriptional regulation of CDKN2A locus. In dividing cells, nucleosomes bound to the CDKN2A locus are trimethylated on lysine residue 28 of histone H3 (HIST1H3A) by the Polycomb repressor complex 2 (PRC2), creating the H3K27Me3 (Me3K-28-HIST1H3A) mark (Bracken et al. 2007, Kotake et al. 2007). The expression of Polycomb constituents of PRC2 (Kuzmichev et al. 2002) - EZH2, EED and SUZ12 - and thereby formation of the PRC2, is positively regulated in growing cells by E2F1, E2F2 and E2F3 (Weinmann et al. 2001, Bracken et al. 2003). H3K27Me3 mark serves as a docking site for the Polycomb repressor complex 1 (PRC1) that contains BMI1 (PCGF4) and is therefore named PRC1.4, leading to the repression of transcription of p16INK4A and p14ARF from the CDKN2A locus, where PCR1.4 mediated repression of p14ARF transcription in humans may be context dependent (Voncken et al. 2005, Dietrich et al. 2007, Agherbi et al. 2009, Gao et al. 2012). MAPKAPK2 and MAPKAPK3, activated downstream of the MAP3K5-p38 MAPK cascade, phosphorylate BMI1 of the PRC1.4 complex, leading to dissociation of PRC1.4 complex from the CDKN2A locus and upregulation of p14ARF transcription (Voncken et al. 2005). AP-1 transcription factor, formed as a result of MAP3K5-JNK signaling, as well as RAS signaling, binds the promoter of KDM6B (JMJD3) gene and stimulates KDM6B expression. KDM6B is a histone demethylase that removes H3K27Me3 mark i.e. demethylates lysine K28 of HIST1H3A, thereby preventing PRC1.4 binding to the CDKN2A locus and allowing transcription of p16INK4A (Agger et al. 2009, Barradas et al. 2009, Lin et al. 2012).


p16INK4A inhibits phosphorylation-mediated inactivation of RB family members by CDK4 and CDK6, leading to cell cycle arrest (Serrano et al. 1993). p14ARF inhibits MDM2-mediated degradation of TP53 (p53) (Zhang et al. 1998), which also contributes to cell cycle arrest in cells undergoing oxidative stress. In addition, phosphorylation of TP53 by MAPKAPK5 (PRAK) activated downstream of MAP3K5-p38 MAPK signaling, activates TP53 and contributes to cellular senescence (Sun et al. 2007).

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