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Chemical activation of divergent protein tyrosine phosphatase domains with cyanine-based biarsenicals
- Source :
- Scientific Reports, Vol 9, Iss 1, Pp 1-14 (2019), Scientific Reports
- Publication Year :
- 2019
- Publisher :
- Nature Publishing Group, 2019.
-
Abstract
- Strategies for the direct chemical activation of specific signaling proteins could provide powerful tools for interrogating cellular signal transduction. However, targeted protein activation is chemically challenging, and few broadly applicable activation strategies for signaling enzymes have been developed. Here we report that classical protein tyrosine phosphatase (PTP) domains from multiple subfamilies can be systematically sensitized to target-specific activation by the cyanine-based biarsenical compounds AsCy3 and AsCy5. Engineering of the activatable PTPs (actPTPs) is achieved by the introduction of three cysteine residues within a conserved loop of the PTP domain, and the positions of the sensitizing mutations are readily identifiable from primary sequence alignments. In the current study we have generated and characterized actPTP domains from three different subfamilies of both receptor and non-receptor PTPs. Biarsenical-induced stimulation of the actPTPs is rapid and dose-dependent, and is operative with both purified enzymes and complex proteomic mixtures. Our results suggest that a substantial fraction of the classical PTP family will be compatible with the act-engineering approach, which provides a novel chemical-biological tool for the control of PTP activity and the study of PTP function.
- Subjects :
- Phosphopeptides
0301 basic medicine
Proteome
Receptor-Like Protein Tyrosine Phosphatases
lcsh:Medicine
Protein tyrosine phosphatase
010402 general chemistry
01 natural sciences
Arsenicals
Article
03 medical and health sciences
chemistry.chemical_compound
Protein Domains
Humans
Point Mutation
Cysteine
Cyanine
Receptor
lcsh:Science
chemistry.chemical_classification
Multidisciplinary
Dose-Response Relationship, Drug
Chemistry
lcsh:R
Cellular signal transduction
Recombinant Proteins
Enzymes
0104 chemical sciences
Enzyme Activation
030104 developmental biology
Enzyme
Protein activation
Biochemistry
Mutagenesis, Site-Directed
lcsh:Q
Protein Tyrosine Phosphatases
Chemical tools
Sequence Alignment
Function (biology)
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....fabc635f2cb164a7c441e94c5092d15e