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MAP3K
Mitogen Activated Protein (MAP) kinase kinase kinase, MAPKKK (or MAP3K) is a serine/threonine-specific protein kinase which acts upon MAP kinase kinase. Subsequently, MAP kinase kinase activates MAP kinase. Several types of MAPKKK can exist but are mainly characterized by the MAP kinases they activate. MAPKKKs are stimulated by a large range of stimuli, primarily environmental and intracellular stressors. MAPKKK is responsible for various cell functions such as cell proliferation, cell differentiation, and apoptosis. The duration and intensity of signals determine which pathway ensues. Additionally, the use of protein scaffolds helps to place the MAPKKK in close proximity with its substrate to allow for a reaction. Lastly, because MAPKKK is involved in a series of several pathways, it has been used as a therapeutic target for cancer, amyloidosis, and neurodegenerative diseases. In humans, there are at least 19 genes which encode MAP kinase kinase kinases: * MAP3K1 (aka MEKK1) * ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MAP3K3
Mitogen-activated protein kinase kinase kinase 3 is an enzyme that in humans is encoded by the ''MAP3K3'' gene, which is located on the long arm of chromosome 17 (17q23.3).MAP3K3 in GeneCards – The Human Gene Compendium. https://www.genecards.org/cgi-bin/carddisp.pl?gene=MAP3K3 Function This gene product is a 626-amino acid polypeptide that is 96.5% identical to mouse MEKK3. Its catalytic domain is closely related to those of several other kinases, including mouse MEKK2, tobacco NPK, and yeast STE11. Northern blot analysis revealed a 4.6-kb transcript that appears to be ubiquitously expressed. MAP3Ks are involved in regulating cell fate in response to external stimuli. MAP3K3 directly regulates the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by activating SEK and MEK1/2 respectively. In cotransfection assays, it enhanced transcription from a nuclear factor kappa-B (NF-κB)-dependent reporter gene, consistent with ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MAP3K7
Mitogen-activated protein kinase kinase kinase 7 (MAP3K7), also known as TAK1, is an enzyme that in humans is encoded by the ''MAP3K7'' gene. Structure TAK1 is an evolutionarily conserved kinase in the MAP3 K family and clusters with the tyrosine-like and sterile kinase families. The protein structure of TAK1 contains an N (residues 1–104)- and C (residues 111–303)-terminus connected through the hinge region (Met 104-Ser 111). The ATP binding pocket is located in the hinge region of the kinase. Additionally, TAK1 has a catalytic lysine (Lys63) in the active site. Crystal structure of TAK1-ATP have shown that ATP forms two hydrogen bonds with residues Ala 107 and Glu 105. Further hydrogen bonding is observed to Asp 175, which is the leading residue of the DFG motif. This residue is thought to interact with Lys 63 through polar interactions and is catalytically important for phosphate transfer to substrate molecules. Critical for the TAK1-TAB1 complex is a helical loop arou ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MAP3K5
Apoptosis signal-regulating kinase 1 (ASK1) also known as mitogen-activated protein kinase 5 (MAP3K5) is a member of MAP kinase family and as such a part of mitogen-activated protein kinase pathway. It activates c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases in a Raf-independent fashion in response to an array of stresses such as oxidative stress, endoplasmic reticulum stress and calcium influx. ASK1 has been found to be involved in cancer, diabetes, rheumatoid arthritis, cardiovascular and neurodegenerative diseases. ''MAP3K5'' gene coding for the protein is located on chromosome 6 at locus 6q22.33. and the transcribed protein contains 1,374 amino acids with 11 kinase subdomains. Northern blot analysis shows that MAP3K5 transcript is abundant in human heart and pancreas. Mechanism of activation Under nonstress conditions ASK1 is oligomerized (a requirement for its activation) through its C-terminal coiled-coil domain (CCC), but remains in an inacti ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MAP3K14
Mitogen-activated protein kinase kinase kinase 14 also known as NF-kappa-B-inducing kinase (NIK) is an enzyme that in humans is encoded by the ''MAP3K14'' gene. Function This gene encodes mitogen-activated protein kinase kinase kinase 14, NIK, which is a serine/threonine protein-kinase. This kinase binds to TRAF2 and stimulates NF-κB activity. It is a critical kinase of the alternative NF-κB activation pathway. It shares sequence similarity with several other MAPKK kinases. It participates in an NF-κB-inducing signalling cascade common to receptors of the tumour-necrosis/nerve-growth factor ( TNF/ NGF) family and to the interleukin-1 type-I receptor. Interactions MAP3K14 has been shown to interact with: * CHUK, * IKK2, and * TRAF2 TNF receptor-associated factor 2 is a protein that in humans is encoded by the ''TRAF2'' gene. Function The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MAP3K2
Mitogen-Activated Protein Kinase Kinase Kinase 2 also known as MEKK2 (MEK/ERK Kinase 2) is an enzyme that in humans is encoded by the ''MAP3K2'' gene. Function The protein encoded by this gene is a member of serine/threonine protein kinase family. This kinase preferentially activates other kinases involved in the MAP kinase signaling pathway. This kinase has been shown to directly phosphorylate and activate IkappaB kinases, and thus plays a role in NF-kappa B signaling pathway. This kinase has also been found to bind and activate protein kinase C -related kinase 2, which suggests its involvement in a regulated signaling process. Activation MEKK2 is activated through homodimerization and subsequent trans-autophosphorylation at MEKK2-S519. MEKK2 is regulated by 14-3-3 proteins which bind to MEKK2-phosphoT283. MEKK2 is regulated by SMYD3 which binds and methylates MEKK2-K260. Interactions MAP3K2 has been shown to interact with: * MAPK8, * MAP2K4, * MAP2K5, * MAP2K7, * ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MAP3K12
Mitogen-activated protein kinase 12 is an enzyme that in humans is encoded by the ''MAP3K12'' gene. Function The protein encoded by this gene is a member of serine/threonine protein kinase family. This kinase contains a leucine-zipper domain, and is predominately expressed in neuronal cells. The phosphorylation state of this kinase in synaptic terminals was shown to be regulated by membrane depolarization via calcineurin. This kinase forms heterodimers with leucine zipper containing transcription factors, such as cAMP responsive element binding protein (CREB) and MYC, and thus may play a regulatory role in PKA or retinoic acid induced neuronal differentiation. Interactions MAP3K12 has been shown to interact with MAPK8IP1, MAP2K7 and MAPK8IP2. Role in development MAP3K12, otherwise known as DLK, can initiate coordinated signalling cascades that culminate in the phosphorylation of C-Jun N-terminal kinases or JNK. Several experiments have implicated this interaction as havin ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
TPL2
Mitogen-activated protein kinase kinase kinase 8 is an enzyme that in humans is encoded by the ''MAP3K8'' gene. Function The gene was identified by its oncogenic transforming activity in cells. The encoded protein is a member of the serine/threonine-specific protein kinase family. This kinase can activate ERK1, ERK2 and p38 MAP kinases. This kinase was shown to activate IkappaB kinases, and thus induce the nuclear production of NF-kappaB. This kinase was also found to promote the production of TNF-alpha and IL-2 during T lymphocyte activation. Studies of a similar gene in rat suggested the direct involvement of this kinase in the proteolysis of NF-kappaB1, p105 (NFKB1). This gene may also start transcription at a downstream in-frame translation start codon, and thus produce an isoform containing a shorter N-terminus. The shorter isoform has been shown to display weaker transforming activity. In mice, the gene is known as TPL2 and is a tumor-suppressor gene whose absence ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MAP3K13
Mitogen-activated protein kinase kinase kinase 13 is an enzyme that in humans is encoded by the ''MAP3K13'' gene. Function The protein encoded by this gene is a member of serine/threonine protein kinase family. This kinase contains a dual leucine-zipper motif, and has been shown to form dimers/oligomers through its leucine-zipper motif. This kinase can phosphorylate and activate MAPK8/JNK, MAP2K7/MKK7, which suggests a role in the JNK signaling pathway. Interactions MAP3K13 has been shown to interact with PRDX3 Thioredoxin-dependent peroxide reductase, mitochondrial is an enzyme that in humans is encoded by the ''PRDX3'' gene. It is a member of the peroxiredoxin family of antioxidant enzymes. Function This gene encodes a protein with antioxidant func .... References Further reading * * * * * EC 2.7.11 {{gene-3-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MAP3K11
Mitogen-activated protein kinase kinase kinase 11 is an enzyme that in humans is encoded by the ''MAP3K11'' gene. Function The protein encoded by this gene is called MLK3 and it is a member of the serine/threonine kinase family. This kinase contains a SH3 domain and a leucine zipper-basic motif. This kinase preferentially activates MAPK8/JNK kinase, and functions as a positive regulator of JNK signaling pathway. This kinase can directly phosphorylate, and activates JNK and p38, and is found to be involved in the transcription activity of AP1 mediated by Rho family GTPases and CDC42. Interactions MAP3K11 has been shown to interact with: * AKT1, * CDC42, * MAPK8IP1, * MAPK8IP2 C-jun-amino-terminal kinase-interacting protein 2 is a protein or the name of the gene that encodes it. The gene is also known as Islet-Brain-2 (IB2). This protein is highly expressed in the brain and is almost always deleted in Phelan-McDermid sy ..., and * SH3RF1. References Further readi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MAP3K10
Mitogen-activated protein kinase kinase kinase 10 is an enzyme that in humans is encoded by the ''MAP3K10'' gene. Function The protein encoded by this gene is a member of the serine/threonine kinase family. This kinase has been shown to activate MAPK8/JNK and MKK4/SEK1, and this kinase itself can be phosphorylated, and thus activated by JNK kinases. This kinase functions preferentially on the JNK signaling pathway, and is reported to be involved in nerve growth factor (NGF) induced neuronal apoptosis. Interactions MAP3K10 has been shown to interact with: * CDC42, * Huntingtin Huntingtin (Htt) is the protein coded for in humans by the ''HTT'' gene, also known as the ''IT15'' ("interesting transcript 15") gene. Mutated ''HTT'' is the cause of Huntington's disease (HD), and has been investigated for this role and also for ..., * KIF3A, * MAPK8IP1, * MAPK8IP2, and * NEUROD1. References Further reading * * * * * * * * * * * * * * * * EC ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tpl2
Mitogen-activated protein kinase kinase kinase 8 is an enzyme that in humans is encoded by the ''MAP3K8'' gene. Function The gene was identified by its oncogenic transforming activity in cells. The encoded protein is a member of the serine/threonine-specific protein kinase family. This kinase can activate ERK1, ERK2 and p38 MAP kinases. This kinase was shown to activate IkappaB kinases, and thus induce the nuclear production of NF-kappaB. This kinase was also found to promote the production of TNF-alpha and IL-2 during T lymphocyte activation. Studies of a similar gene in rat suggested the direct involvement of this kinase in the proteolysis of NF-kappaB1, p105 (NFKB1). This gene may also start transcription at a downstream in-frame translation start codon, and thus produce an isoform containing a shorter N-terminus. The shorter isoform has been shown to display weaker transforming activity. In mice, the gene is known as TPL2 and is a tumor-suppressor gene whose absence ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |