Author
Wenqing Xu
Other affiliations: Harvard University, Boston Children's Hospital, Massachusetts Institute of Technology ...read more
Bio: Wenqing Xu is an academic researcher from University of Washington. The author has contributed to research in topics: Wnt signaling pathway & Protein phosphatase 2. The author has an hindex of 38, co-authored 66 publications receiving 8329 citations. Previous affiliations of Wenqing Xu include Harvard University & Boston Children's Hospital.
Papers published on a yearly basis
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TL;DR: The structure of a large fragment of the c-SRC tyrosine kinase, comprising the regulatory and kinase domains and the carboxy-terminal tail, has been determined and shows how appropriate cellular signals, or transforming mutations in v-Src, could break these interactions to produce an open, active kinase.
Abstract: The structure of a large fragment of the c-Src tyrosine kinase, comprising the regulatory and kinase domains and the carboxy-terminal tall, has been determined at 1.7 A resolution in a closed, inactive state. Interactions among domains, stabilized by binding of the phosphorylated tail to the SH2 domain, lock the molecule in a conformation that simultaneously disrupts the kinase active site and sequesters the binding surfaces of the SH2 and SH3 domains. The structure shows how appropriate cellular signals, or transforming mutations in v-Src, could break these interactions to produce an open, active kinase.
1,403 citations
TL;DR: Four additional c-Src structures in which this segment adopts an ordered but inhibitory conformation are reported, in which the ordered activation loop forms an alpha helix that stabilizes the inactive conformation of the kinase domain, blocks the peptide substrate-binding site, and prevents Tyr-416 phosphorylation.
851 citations
TL;DR: This work suggests a working model for the destruction complex based on the existing structural and experimental data, and focuses on the questions that this model and other studies have raised about the function of the complex in both the normal and Wnt-inhibited states.
Abstract: At the heart of the canonical Wnt signaling pathway is the β-catenin destruction complex, which functions in the absence of Wnt signaling to keep the cytosolic and nuclear levels of β-catenin very low by promoting the phosphorylation and ubiquitination of β-catenin. Structural studies, combined with other experimental approaches, have begun to provide important insights into the mechanism of the destruction complex. We suggest a working model for the destruction complex based on the existing structural and experimental data, and focus on the questions that this model and other studies have raised about the function of the complex in both the normal and Wnt-inhibited states.
618 citations
TL;DR: It is shown that enzymatic activity of Salmonella typhimurium PhoQ is directly activated by antimicrobial peptides.
518 citations
TL;DR: The crystal structure of an AB′C heterotrimeric PP2A holoenzyme reveals that the HEAT repeats of the scaffold A subunit form a horseshoe-shaped fold, holding the catalytic C and regulatory B′ subunits together on the same side.
Abstract: Protein phosphatase 2A (PP2A) is a principal Ser/Thr phosphatase, the deregulation of which is associated with multiple human cancers, Alzheimer's disease and increased susceptibility to pathogen infections. How PP2A is structurally organized and functionally regulated remains unclear. Here we report the crystal structure of an AB'C heterotrimeric PP2A holoenzyme. The structure reveals that the HEAT repeats of the scaffold A subunit form a horseshoe-shaped fold, holding the catalytic C and regulatory B' subunits together on the same side. The regulatory B' subunit forms pseudo-HEAT repeats and interacts with the C subunit near the active site, thereby defining substrate specificity. The methylated carboxy-terminal tail of the C subunit interacts with a highly negatively charged region at the interface between A and B' subunits, suggesting that the C-terminal carboxyl methylation of the C subunit promotes B' subunit recruitment by neutralizing charge repulsion. Together, our structural results establish a crucial foundation for understanding PP2A assembly, substrate recruitment and regulation.
432 citations
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TL;DR: There is growing evidence that aging involves, in addition, progressive changes in free radical-mediated regulatory processes that result in altered gene expression.
Abstract: At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, how...
9,131 citations
TL;DR: Understanding of the complex signaling networks downstream from RTKs and how alterations in these networks are translated into cellular responses provides an important context for therapeutically countering the effects of pathogenic RTK mutations in cancer and other diseases.
7,056 citations
TL;DR: The data reveal that multiple extracellular, cytoplasmic, and nuclear regulators intricately modulate Wnt signaling levels, and that receptor-ligand specificity and feedback loops help to determine WNT signaling outputs.
Abstract: Tight control of cell-cell communication is essential for the generation of a normally patterned embryo. A critical mediator of key cell-cell signaling events during embryogenesis is the highly conserved Wnt family of secreted proteins. Recent biochemical and genetic analyses have greatly enriched our understanding of how Wnts signal, and the list of canonical Wnt signaling components has exploded. The data reveal that multiple extracellular, cytoplasmic, and nuclear regulators intricately modulate Wnt signaling levels. In addition, receptor-ligand specificity and feedback loops help to determine Wnt signaling outputs. Wnts are required for adult tissue maintenance, and perturbations in Wnt signaling promote both human degenerative diseases and cancer. The next few years are likely to see novel therapeutic reagents aimed at controlling Wnt signaling in order to alleviate these conditions.
5,129 citations
TL;DR: A remarkable interdisciplinary effort has unraveled the WNT (Wingless and INT-1) signal transduction cascade over the last two decades, finding that Germline mutations in the Wnt pathway cause several hereditary diseases, and somatic mutations are associated with cancer of the intestine and a variety of other tissues.
5,042 citations
TL;DR: Some key aspects of Wnt/beta-catenin signaling in human diseases including congenital malformations, cancer, and osteoporosis are highlighted, and potential therapeutic implications are discussed.
4,926 citations