PTP1B: From the sidelines to the front lines!

@article{Tonks2003PTP1BFT,
  title={PTP1B: From the sidelines to the front lines!},
  author={Nicholas K. Tonks},
  journal={FEBS Letters},
  year={2003},
  volume={546}
}
  • N. Tonks
  • Published 3 July 2003
  • Biology
  • FEBS Letters
PTP1B: A simple enzyme for a complex world
TLDR
A review of the emergence of PTP1B through evolution, and at the cell and systemic levels how it is controlled physiologically is explored, as well as its involvement in metabolic syndromes and cancer.
Bidentate inhibitors of protein tyrosine phosphatases.
TLDR
Bidentate inhibitors are small-molecular-weight compounds with the ability to bind to both the active site and a non-conserved secondary phosphate binding site that were initially discovered in protein tyrosine phosphatase 1B, and, hence, most of the bidentate inhibitor reported in this review are PTP1B inhibitors.
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Potent and specific PTP inhibitors could significantly facilitate functional analysis of the PTPs in complex cellular signal transduction pathways and may constitute valuable therapeutics in the treatment of several human diseases.
Covalent inhibition of protein tyrosine phosphatases.
TLDR
In vivo and in vitro inactivation of various PTPs by small molecule-containing electrophiles, such as Michael acceptors, α-halo ketones, epoxides, and isothiocyanates, etc, are discussed and potential strategies to transform these electrophile into isozyme selective covalent PTP inhibitors are suggested.
PTP1B and TC-PTP: novel roles in immune-cell signaling.
TLDR
This review will focus on the substrate specificities of PTP1B and TC-PTP and their roles in immune cell signaling, and will discuss some new data implicating PTP2B and T-cell PTP in myeloid development.
The role of pseudophosphatases as signaling regulators.
  • Shantá D. Hinton
  • Biology, Chemistry
    Biochimica et biophysica acta. Molecular cell research
  • 2019
Recent advance on PTP1B inhibitors and their biomedical applications.
Protein tyrosine phosphatases – from housekeeping enzymes to master regulators of signal transduction
TLDR
This review is a personal perspective on the development of the understanding of the protein tyrosine phosphatase family of enzymes and hopes will illustrate the fundamental importance of these enzymes in the control of signal transduction.
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References

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Crystal Structure of PTP1B Complexed with a Potent and Selective Bidentate Inhibitor*
TLDR
The data suggest that potent, yet highly selective, PTP1B inhibitory agents can be acquired by targeting the area defined by residues Lys-41, Arg-47, and Asp-48, in addition to the previously identified second aryl phosphate-binding pocket.
Protein kinases — the major drug targets of the twenty-first century?
  • P. Cohen
  • Biology
    Nature reviews. Drug discovery
  • 2002
TLDR
A personal view of some of the most important advances that have shaped this field of protein kinases, after G-protein-coupled receptors.
Acquisition of a Specific and Potent PTP1B Inhibitor from a Novel Combinatorial Library and Screening Procedure*
TLDR
A combinatorial approach that is designed to target both the active site and a unique peripheral site in PTP1B, demonstrating that it is possible to acquire potent, yet highly selective inhibitors for individual members of the large PTPase family of enzymes.
TYK2 and JAK2 Are Substrates of Protein-tyrosine Phosphatase 1B*
TLDR
It is demonstrated that (E/D)-pY-pY-(R/K) is a consensus substrate recognition motif for PTP1B and that the substrate recognition site within theses kinases is similar to the site of dephosphorylation previously identified within the insulin receptor.
Residue 259 Is a Key Determinant of Substrate Specificity of Protein-tyrosine Phosphatases 1B and α*
TLDR
It is demonstrated that the key selectivity-determining residue in PTPα plays a dual role leading to restricted substrate recognition and reduced catalytic activity, which may indicate that PTP α regulates highly selective signal transduction processes.
Structure of protein tyrosine phosphatase 1B in complex with inhibitors bearing two phosphotyrosine mimetics.
TLDR
The crystal structure of PTP1B complexed with two non-peptidyl inhibitors, 4 and 5, both of which contain two aryl difluoromethylenephosphonic acid groups, a nonhydrolyzable phosphate mimetic is determined and the selectivity of these two inhibitors was examined.
Development of "substrate-trapping" mutants to identify physiological substrates of protein tyrosine phosphatases.
TLDR
The results suggest that the EGF receptor is a bona fide substrate for PTP 1B in vivo and that one important function of PTP1B is to prevent the inappropriate, ligand-independent, activation of newly synthesized EGF receptors in the endoplasmic reticulum.
Imaging Sites of Receptor Dephosphorylation by PTP1B on the Surface of the Endoplasmic Reticulum
TLDR
Most of the RTKs activated at the cell surface showed interaction with PTP1B after internalization, establishing that RTK activation and inactivation are spatially and temporally partitioned within cells.
Structural basis for inhibition of the protein tyrosine phosphatase 1B by phosphotyrosine peptide mimetics.
TLDR
Structures of PTP1B in complex with the (difluoronaphthylmethyl)phosphonic acid derivatives reveal that substitutions of the naphthalene ring modulate the mode of inhibitor binding to the catalytic site and provide the potential for enhanced inhibitor affinity and the generation of P TP-specific inhibitors.
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