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61.
62.
Protein tyrosine phosphatases regulate signal transduction pathways involving tyrosine phosphorylation and have been implicated in the development of cancer, diabetes, rheumatoid arthritis and hypertension. Increasing evidence suggests that the cellular redox state is involved in regulating tyrosine phosphatase activity through the reversible oxidization of the catalytic cysteine to sulphenic acid (Cys-SOH). But how further oxidation to the irreversible sulphinic (Cys-SO2H) and sulphonic (Cys-SO3H) forms is prevented remains unclear. Here we report the crystal structures of the regulatory sulphenic and irreversible sulphinic and sulphonic acids of protein tyrosine phosphatase 1B (PTP1B), an important enzyme in the negative regulation of the insulin receptor and a therapeutic target in type II diabetes and obesity. We also identify a sulphenyl-amide species that is formed through oxidation of its catalytic cysteine. Formation of the sulphenyl-amide causes large changes in the PTP1B active site, which are reversible by reduction with the cellular reducing agent glutathione. The sulphenyl-amide is a protective intermediate in the oxidative inhibition of PTP1B. In addition, it may facilitate reactivation of PTP1B by biological thiols and signal a unique state of the protein. 相似文献
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64.
The murine epidermis contains resident T cells that express a canonical γδ TCR and arise from fetal thymic precursors. These
cells are termed dendritic epidermal T cells (DETC) and use a TCR that is restricted to the skin in adult animals. DETC produce
low levels of cytokines and growth factors that contribute to epidermal homeostasis. Upon activation, DETC can secrete large
amounts of inflammatory molecules which participate in the communication between DETC, neighboring keratinocytes and langerhans
cells. Chemokines produced by DETC may recruit inflammatory cells to the epidermis. In addition, cell–cell mediated immune
responses also appear important for epidermal–T cell communication. Information is provided which supports a crucial role
for DETC in inflammation, wound healing, and tumor surveillance. 相似文献
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66.
Yang X Ongusaha PP Miles PD Havstad JC Zhang F So WV Kudlow JE Michell RH Olefsky JM Field SJ Evans RM 《Nature》2008,451(7181):964-969
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68.
A C Gough J S Miles N K Spurr J E Moss A Gaedigk M Eichelbaum C R Wolf 《Nature》1990,347(6295):773-776
The mammalian cytochrome P450-dependent monooxygenase system is involved in the metabolism of drugs and chemical carcinogens. The role of these enzymes in toxicological response is exemplified by an autosomal recessive polymorphism at the cytochrome P450 CYP2D6 debrisoquine hydroxylase locus which results in the severely compromised metabolism of at least 25 drugs, and which in some cases can lead to life-threatening side-effects. In addition, this polymorphism, which affects 8-10% of the caucasian population, has been associated with altered susceptibility to lung and bladder cancer. Here we report the identification of the primary mutation responsible for this metabolic defect and the development of a simple DNA-based genetic assay to allow both the identification of most individuals at risk of drug side-effects and clarification of the conflicting reports on the association of this polymorphism with cancer susceptibility. 相似文献
69.
Antibiotic bioassay by flow microcalorimetry 总被引:1,自引:0,他引:1
A. E. Beezer R. J. Miles Elizabeth J. Shaw Lynne Vickerstaff 《Cellular and molecular life sciences : CMLS》1980,36(9):1051-1052
Summary A rapid, sensitive microcalorimetric bioassay of good reproducibility has been developed for the antibiotics penicillin-G, carbenicillin, ampicillin and cefoxitin. The use of growing organisms as responding agents allows discussion of the results for systems which may involve biological fluids.Acknowledgment. We thank the Department of Health and Social Security for a grant to support this work. 相似文献
70.
Letter: formation of nitrosamines in a meat curing mixture 总被引:3,自引:0,他引:3