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61.
Hasmik Keshishian E Robert McDonald III Filip Mundt Randy Melanson Karsten Krug Dale A Porter Luke Wallace Dominique Forestier Bokang Rabasha Sara E Marlow Judit JaneValbuena Ellen Todres Harrison Specht Margaret Lea Robinson Pierre M Jean Beltran Ozgun Babur Meagan E Olive Javad Golji Eric Kuhn Michael Burgess Melanie A MacMullan Tomas Rejtar Karen Wang DR Mani Shankha Satpathy Michael A Gillette William R Sellers Steven A Carr 《Molecular systems biology》2021,17(9)
Reliable methods to quantify dynamic signaling changes across diverse pathways are needed to better understand the effects of disease and drug treatment in cells and tissues but are presently lacking. Here, we present SigPath, a targeted mass spectrometry (MS) assay that measures 284 phosphosites in 200 phosphoproteins of biological interest. SigPath probes a broad swath of signaling biology with high throughput and quantitative precision. We applied the assay to investigate changes in phospho‐signaling in drug‐treated cancer cell lines, breast cancer preclinical models, and human medulloblastoma tumors. In addition to validating previous findings, SigPath detected and quantified a large number of differentially regulated phosphosites newly associated with disease models and human tumors at baseline or with drug perturbation. Our results highlight the potential of SigPath to monitor phosphoproteomic signaling events and to nominate mechanistic hypotheses regarding oncogenesis, response, and resistance to therapy. 相似文献
62.
Thirty-four cytochrome P-450 sequences from one bacterial and six
vertebrate species have been aligned with the aid of a computer alignment
algorithm. Phylogenetic trees were constructed using the
unweighted-pair-group and neighbor-joining methods. The two trees differed
at only a single branch point near the base of the tree. The cytochrome
P-450 superfamily of proteins clustered into eight families and contained
16 gene-duplication events. The first gene duplication occurred
approximately 1,360 Myr before the present (Mybp) and gave rise to
cytochrome P-450s found in two different cellular organelles, the
mitochondria and the endoplasmic reticulum. Both groups utilize cholesterol
or its metabolites as substrates, implying that cholesterol existed greater
than 1,360 Mybp. The fourth gene duplication (approximately 900 Mybp) gave
rise to the drug-metabolizing P-450s. These proteins aid in the
detoxification of foreign chemicals, as opposed to the metabolism of
endogenous compounds. The importance of the capacity to metabolize drugs is
reflected in 11 further gene duplications occurring in this lineage. The
first occurred approximately 800 Mybp and gave rise to the two major P-450
families, the phenobarbital and 3-methylcholanthrene families. An apparent
increase in the rate of cytochrome P-450 evolution is noted between the
bird-mammal divergence (300 Mybp) and the mammalian radiation (75 Mybp).
相似文献
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