instruction:
Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.
question:
Specific outcomes upon activation of the c-Jun N-terminal kinase (JNK) pathway critically depend on the intensity and duration of signal transmission. Dual-specificity phosphatases (DUSPs) play a very important role in these events by modulating the extent of JNK phosphorylation and activation and thus regulating cellular responses to stress. M3/6 (DUSP8) is one of the dual-specificity protein phosphatases with distinct specificity towards JNK. It has been shown that M3/6 itself is phosphorylated by JNK upon stimulation with arsenite, but the role of this phosphorylation has not been investigated. In this study, we mapped JNK-induced phosphorylation sites on M3/6 using mass spectrometry. Phosphorylated residues Ser 515, Thr 518 and Ser 520 were identified and site-directed mutagenesis was employed to investigate their role. Upon arsenite stimulation, M3/6 mutated at these sites exhibited decreased phosphorylation compared to the wild-type protein. No difference was observed in terms of the enzyme's in vitro phosphatase activity, its substrate specificity towards JNK isoforms, its interactions with JNK and the scaffold family of JNK-interacting proteins (JIPs), its stability or its subcellular localization. Interestingly, expression of M3/6 phosphorylation mutants delayed the time-course of JNK phosphorylation and activation by arsenite. We propose that phosphorylation of the M3/6 phosphatase by JNK in response to stress stimuli results in attenuation of phosphatase activity and acceleration of JNK activation.
answer:
Which protein is affected by dusp8 activation?


question:
Protein kinases (PKs) and lipid kinases (LKs) are good choices for targets of signal transduction therapy as these enzymes are involved in signaling pathways, and are often related to the pathogenesis of lymphoid malignancies. The attractiveness of PKs and LKs as drug able targets is enhanced by the fact that they are enzymes whose biological activity can be turned off by drugs that block their catalytic site. In the last few years small molecular kinase inhibitors (KIs) have been synthesized and become available for preclinical studies and clinical trials. The first KI, introduced into clinical practice in 1998, was imatinib mesylate, which became the first choice drug in chronic myeloid leukemia. More recently, several KIs have been developed to target the proximal B-cell receptor (BCR) signaling pathway including spleen tyrosine kinase inhibitor (Fostamatinib) and Bruton's tyrosine kinase inhibitors (Ibrutinib, AVL-263). These agents are currently evaluated in early clinical trials in chronic lymphocytic leukemia (CLL) and other diseases. Cyclin-dependent kinase (Cdk) inhibitors, flavopiridol (alvocidib), BMS-387032 (SNS-032), sunitinib and sorafenib are currently under evaluation in clinical trials for relapsed/refractory CLL. Multi-tyrosine kinase inhibitors including vandetanib (ZD6474) bosutinib (SKI-606), TKI258 (CHIR-258), pazopanib (GW786034) and axitinib (AG013736) have been also developed for the treatment of lymphoid malignancies. Phosphatidylinositol 3-kinases (PI3K ) are a family of lipid kinases that mediate signals from cell surface receptors. CAL-101 (GS-1101) is an oral PI3K-specific inhibitor which has shown preclinical and clinical activity against CLL. This article summarizes recent achievements in the mechanism of action, pharmacological properties and clinical activity and toxicity of PK and LK inhibitors in CLL.
answer:
What is the name of Bruton's tyrosine kinase inhibitor that can be used for treatment of chronic lymphocytic leukemia?


question:
Topographic maps represent the locations of geographical features, such as hills and valleys. Topographic maps use contour lines to show different elevations. A contour line is a line of equal elevation. If you walk along a contour line you will not go uphill or downhill. Topographic maps are also called contour maps. The rules of topographic maps are: Each line connects all points of a specific elevation. Contour lines never cross since a single point can only have one elevation. Every fifth contour line is bolded and labeled. Adjacent contour lines are separated by a constant difference in elevation (such as 20 ft or 100 ft). The difference in elevation is the contour interval, which is indicated in the map legend. Scales indicate horizontal distance and are also found on the map legend. Old Faithful erupting, Yellowstone Na- tional Park. While the Figure 1.1 isnt exactly the same view as the map at the top of this concept, it is easy to see the main features. Hills, forests, development, and trees are all seen around Old Faithful. A bathymetric map is like a topographic map with the contour lines representing depth below sea level, rather than height above. Numbers are low near sea level and become higher with depth. Kilauea is the youngest volcano found above sea level in Hawaii. On the flank of Kilauea is an even younger volcano called Loihi. The bathymetric map pictured in the Figure 1.2 shows the form of Loihi. Loihi volcano growing on the flank of Kilauea volcano in Hawaii. Black lines in the inset show the land surface above sea level and blue lines show the topography below sea level. A geologic map of the region around Old Faithful, Yellowstone National Park. A geologic map shows the geological features of a region (see Figure 1.3 for an example). Rock units are color- coded and identified in a key. Faults and folds are also shown on geologic maps. The geology is superimposed on a topographic map to give a more complete view of the geology of the region. Click image to the left or use the URL below. URL:
answer:

this type of map shows rock units and features like faults and folds.