Rabbit Anti-Human PXK (a.a. 1-352) Polyclonal antibody

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an endogenous secreted peptide and, in preclinical studies, preferentially induces apoptosis in tumor cells rather than in normal cells. The acquisition of resistance in cells exposed to TRAIL or its mimics limits their clinical efficacy. Because kinases are intimately involved in the regulation of apoptosis, we systematically characterized kinases involved in TRAIL signaling. Using RNA interference (RNAi) loss-of-function and cDNA overexpression screens, we identified 169 protein kinases that influenced the dynamics of TRAIL-induced apoptosis in the colon adenocarcinoma cell line DLD-1. We classified the kinases as sensitizers or resistors or modulators, depending on the effect that knockdown and overexpression had on TRAIL-induced apoptosis. Two of these kinases that were classified as resistors were PX domain-containing serine/threonine kinase (PXK) and AP2-associated kinase 1 (AAK1), which promote receptor endocytosis and may enable cells to resist TRAIL-induced apoptosis by enhancing endocytosis of the TRAIL receptors. We assembled protein interaction maps using mass spectrometry-based protein interaction analysis and quantitative phosphoproteomics. With these protein interaction maps, we modeled information flow through the networks and identified apoptosis-modifying kinases that are highly connected to regulated substrates downstream of TRAIL. The results of this analysis provide a resource of potential targets for the development of TRAIL combination therapies to selectively kill cancer cells.

The effect of various N, P and K supply levels and their combinations on the development, yield and yield components of poppy (cv. Kek Duna) was studied in the 10(th) year of a long-term mineral fertilisation experiment set up on loamy chernozem soil with lime deposits. A correlation was sought between the mass of the poppy plants and other parameters. The soil of the growing site contained 3 % humus, 5 % CaCO3 and 20 % clay in the ploughed layer and was poorly supplied with P and Zn and moderately well with N and K. The experiment included 4Nx4Px4K=64 treatments in 2 replications, giving a total of 128 plots. The mineral fertilisers were applied in the form of calcium ammonium nitrate containing 25 % N, superphosphate (18 % P) and potassium chloride (50 % K). The groundwater was at a depth of 13-15 m and the area was liable to drought. The main results were as follows: 1. The PxK interactions were already pronounced in the early rosette phase of development, and flowering was initiated and completed 7-10 days earlier on well-supplied soil. In the dry year of 1983 a seed yield of 200 kg/ha was obtained on soil unfertilised for 10 years, while the yield was 800 kg/ha in the optimum N1P1K2 treatment. In this same treatment the capsule yield rose from 182 kg/ha to 586 kg/ha and the stalk yield from 708 kg/ha to 2084 kg/ha. 2. An optimum supply level was provided by 177 mg/kg AL-P2O5 and 232 mg/kg AL-K2O in the ploughed layer. A balanced PK supply was able to counteract the negative effect of drought to a considerable extent and even over-fertilisation did not cause a significant yield depression. Excessive N, however, led to a significant 10 % reduction in plant number. 3. The total air-dry yield amounted to 1.3 t/ha on the control plot and to 4.3 t/ha in the N1P1K2 treatment. On average the roots made up 16 %, the stalks 49 %, the capsules 15 % and the seed 20 % of the air-dry yield at harvest. 4. An improvement in the PK supplies also led to an increase in the capsule mass, the number of capsules per plant and the number of capsules per hectare. P fertilisation had a decisive influence on the yield components: the 1000-seed mass rose on average by 15 %, the number of seeds per capsule by 37 %, the seed yield per capsule by 52 % and the seed yield per plant by 106 %. 5. The individual plant production showed differences of an order of magnitude. In an 80-100 cm stand, plants measuring only 50-60 cm arc unable to satisfy their light and nutrient requirements, leading to a drastic reduction in capsule number, capsule diameter, 1000-seed mass, seed mass per capsule, seed oil % and oil and morphine base yield. The analysis of individual plants showed that poorly developed status is also indicated by low P and K concentrations or uptake.