Disease relevance of Map3k10

• Positional cloning implicated the serine-threonine kinase WNK4 in this process; clustered mutations in PRKWNK4, encoding WNK4, cause hypertension and hyperkalemia (pseudohypoaldosteronism type II, PHAII) by altering renal NaCl and K+ handling [1].
• Acute activation of the serine-threonine kinase Akt is cardioprotective and reduces both infarction and dysfunction after ischemia/reperfusion injury (IRI) [2].
• CONCLUSIONS: Long-term treatment with a combination of agents that selectively inhibit two intracellular signal-transduction enzymes, such as the PKAI serine-threonine kinase and the EGFR tyrosine kinase, has anticancer activity in vivo, reflected by suppression of tumor proliferation and angiogenesis, with no signs of toxicity [3].
• Mutations in the serine-threonine kinase WNK4 [with no lysine (K) 4] cause pseudohypoaldosteronism type II, a Mendelian disease featuring hypertension with hyperkalemia [4].
• Tpl-2/Cot proto-oncogene encodes a serine threonine kinase and was initially cloned as a provirus insertion site in MoMuLV-induced T cell lymphomas in rats [5].

High impact information on Map3k10

• Protein kinase casein kinase II (Ck2) is a cyclic-AMP and calcium-independent serine-threonine kinase that is composed of two catalytic subunits (alpha and alpha') and two regulatory beta-subunits [6].
• Growth factors can promote cell survival by activating the phosphatidylinositide-3'-OH kinase and its downstream target, the serine-threonine kinase Akt [7].
• Phosphorylation of the serine-threonine kinase Akt, which activates eNOS, was substantially reduced in sinusoidal endothelial cells from injured livers [8].
• Activation of Rho may be linked directly to a serine-threonine kinase pathway [9].
• Activation of the serine-threonine kinase p34cdc2 at an inappropriate time during the cell cycle leads to cell death that resembles apoptosis [10].

Chemical compound and disease context of Map3k10

• The treatment of Swiss mice with himachalol (200 mg kg-1, po) once a day, for 7 days, provided 60% protection concomitantly with increased MST (15 days) against invasive aspergillosis [11].

Biological context of Map3k10

• A retroviral oncogene, akt, encoding a serine-threonine kinase containing an SH2-like region [12].
• Although Akt is a serine-threonine kinase, part of its regulatory region is similar to the Src homology-2 domain, a structural motif characteristic of cytoplasmic tyrosine kinases that functions in protein-protein interactions [12].
• The serine-threonine kinase Akt has been implicated in inhibiting cell death induced by different stimuli including growth factor withdrawal, cell cycle discordance, DNA damage, and loss of cell adhesion in different cell types [13].
• The positions of introns in the intracellular domain are almost identical to those of the mouse serine-threonine kinase receptor TSK-7L [14].
• In adipose tissue, insulin controls glucose and lipid metabolism through the intracellular mediators phosphatidylinositol 3-kinase and serine-threonine kinase AKT [15].

Anatomical context of Map3k10

• Expression of mixed lineage kinase 2 in germ cells of the testis [16].
• Sequence analysis of v-akt and biochemical characterization of its product revealed that it codes for a protein kinase C-related serine-threonine kinase whose cellular homolog is expressed in most tissues, with the highest amount found in thymus [12].
• Here we report that the serine-threonine kinase MINK selectively connects the T cell receptor to a signaling pathway that mediates negative but not positive selection [17].
• The serine-threonine kinase Raf protein is phosphorylation-activated by a large array of agonists including plasma membrane and cytoplasmic tyrosine kinases but has not previously been associated with the steroid superfamily of mediators [18].
• Mice in this group rejected their grafts acutely (MST 12 days), suggesting indeed that stem cells might be very important in the success of this model [19].

Associations of Map3k10 with chemical compounds

• Here we show that the serine-threonine kinase protein kinase C epsilon (PKCepsilon) functions as a signal integrator between cytokine and integrin signalling pathways [20].
• In the liver, insulin controls both lipid and glucose metabolism through its cell surface receptor and intracellular mediators such as phosphatidylinositol 3-kinase and serine-threonine kinase AKT [21].
• Deaminative cleavage of MST heparin by HNO2 at pH 1.5 released disaccharides that were similar in composition to those obtained from commercial heparin, except that disaccharides containing 3,6-O-desulfated GlcN units were not found [22].
• During mitosis, PLK is phosphorylated on serine, and its serine threonine kinase function is activated at a time close to that of p34cdc2 [23].
• Treatment of donor, hand-picked islets with a mixture of cross-reactive anti-Ia antibodies and complement without cyclosporin-A therapy did not prolong the survival of islet allografts (MST, 6.5 +/- 0.4 days versus 7.0 +/- 0.5 days in controls) [24].

Enzymatic interactions of Map3k10

• AKT serine threonine kinase phosphorylates GATA-1S310 in vitro and in erythroid cells and enhances GATA-1 transcriptional activity [25].
• Protein kinase C is a serine threonine kinase which phosphorylates vimentin and through this mechanism causes intermediate filament disassembly [26].

Regulatory relationships of Map3k10

• A screen for upstream activators of NF-kappaB identified a novel serine-threonine kinase capable of activating NF-kappaB and inducing apoptosis [27].
• We undertook a study to determine if the serine-threonine kinase-encoding v-mos oncogene regulated the expression of the urokinase-type plasminogen activator [28].

Other interactions of Map3k10

• It was previously shown that the serine threonine kinase Akt is a substrate of PTK6 and that PTK6-mediated phosphorylation of Akt on tyrosine resulted in inhibition of Akt activity [29].
• Hypertrophy of Pten-deficient neurons required the activity of the serine-threonine kinase mTor. mTor is a master regulator of cell and organ growth which can trigger a cascade of downstream signaling pathways involving, in part, components of the translational machinery, including S6k1 and its substrate the ribosomal protein S6 [30].
• Cdk5 is a serine-threonine kinase, the activity of which is dependent on its activating subunits p35 and p39 [31].
• The type II receptors for TGF-beta and activin contain putative serine-threonine kinase domains [32].
• PLC-gamma also coimmunoprecipitated with two other putative receptor substrates, the serine-threonine kinase Raf-1 and the 85-kilodalton phosphatidylinositol-3' kinase, presumably through its association with the ligand-activated receptor [33].

Analytical, diagnostic and therapeutic context of Map3k10

• Members of the TGF-beta superfamily of signalling molecules work by activating transmembrane receptors with phosphorylating activity (serine-threonine kinase receptors); these in turn phosphorylate and activate SMADs, a class of signal transducers [34].
• In wild-type cells, we found CARD9 inducibly associated with both the intracellular 'biosensor' Nod2 and the serine-threonine kinase RICK [35].
• The control group had MST of 7.3 days [36].
• As with fully xenogeneic chimeras (rat-->mouse), synchronous donor-specific F344 rat (Rt1A1) islet xenografts were significantly prolonged (MST > 139 days) in mixed xenogeneic (mouse+rat-->mouse) chimeras, while MHC-disparate third-party WF rat (Rt1Au) grafts were rejected (MST = 21.2 days) [37].
• However, when the primary heart graft was removed 50 days after transplantation, a time point when tolerance to donor alloantigens was demonstrable in vivo, tolerance was lost 200 days later (MST of second C57 heart grafts 31 days) [38].

References