Dataset Information

Ultra-deep human phosphoproteome reveals different regulatory nature of Tyr and Ser/Thr-based signaling

ABSTRACT: Regulatory protein phosphorylation controls nearly every normal and pathophysiological signaling system in eukaryotic cells. Despite great advances in mass spectrometry based-proteomics, the total number, localization and site-specific stoichiometry of this post-translational modification (PTM) are unknown. Here we develop stringent experimental and computational workflow, capable of mapping more than 50,000 distinct phosphorylated peptides in a single human cancer cell line. Label-free quantitation determined very high stoichiometries in mitosis or growth factor signaling and more than three-quarters of cellular proteins were detected as phosphoproteins. The proportion of phospho-Tyr drastically decreases as coverage of the phosphoproteome increases, whereas Ser/Thr sites only saturate for technical reasons. Tyrosine phosphorylation is maintained at especially low stoichiometric levels in the absence of specific signaling events. Unexpectedly, it is statistically enriched on higher abundance proteins and this correlates with the substrate Km values of tyrosine kinases. Our data suggests that P-Tyr should be considered a functionally separate PTM of eukaryotic proteomes.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Matthias Mann

PROVIDER: MSV000080701 | MassIVE | Tue Mar 28 21:28:00 BST 2017

SECONDARY ACCESSION(S): PXD000612

REPOSITORIES: MassIVE

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Wound dressings with electrically conductive layers

JUHASZ LASZLO

19861209

PCT No. PCT/GB86/00218 Sec. 371 Date Dec. 9, 1986 Sec. 102(e) Date Dec. 9, 1986 PCT Filed Apr. 18, 1986 PCT Pub. No. WO86/05971 PCT Pub. Date Oct. 23, 1986.An integral anti-bacterial wound dressing, which comprises, five layers which are, in order (except that layers and 3 and 4 may be in either order), (1) a first layer of a permeable material; (2) a layer of a semi-permeable material; (3) a layer of an electrically-conductive material, in the form of an open mesh; (4) a layer of charcoal fabri ...[more]

PMID: US4817594

Similar Datasets

Project description:Dietary tyrosine regulating melanoma progression has been well-recognized. However, whether tyrosine-based melanin anabolism contributes to pulmonary and cerebral organotropic colonization of melanoma remains elusive. Furthermore, how to inhibit multi-organ metastasis by interfering tyrosinase activity of melanoma cells and function of immunocytes needs to be designed and validated. Patients derived melanoma cells and mouse B16 melanoma cells with different pigment were employed in this investigation. Tyrosine content dynamics in tumors and multiple organs during the melanoma progression were monitored, and tyrosine-based melanin synthesis ability of melanoma cells derived from multi-organ were detected. Additionally, we also adopted the RNA-seq, flowcytometry, real-time PCR and composite metastasis mouse model to analyze organotropic colonization and to design therapeutic strategies. B16 melanoma cells with high activity of tyrosinase and sensitivity of tyrosine utilization for melanin synthesis (Tyr-H cells) easily colonized in the lung, while B16 melanoma cells without above characteristics (Tyr-L cells) exhibited potent proliferation in the brain. Mechanistically, Tyr-H cells recruited and trained neutrophils and macrophages to build up the pulmonary metastatic niche dependent on highly secreted CXCL1 and CXCL2 and an excess melanosome accumulation-induced cell death. Tyr-L cells enhanced PD-L1 expression in tumor-infiltrated macrophages when they are progressing in the brain. Accordingly, intervention of tyrosinase activity (2-Ethoxybenzamide or hydroquinone), together with inhibitors to phagocytosis (GSK343) or chemotaxis (SB225002) suppress organotropic colonization and significantly improve the survival of immune checkpoint blockade (PD1 antibody) treated melanoma bearing mice. The heterogeneity of melanoma cells in utilization of tyrosine is associated with organotropic colonization, providing the basis for developing strategies to combat melanoma and prevent their metastasis.