scholarly journals Protein tyrosine phosphatases and signalling

2005 ◽  
Vol 185 (1) ◽  
pp. 19-33 ◽  
Author(s):  
Andrew W Stoker
Keyword(s):  
Tyrosine Kinases ◽  
Current Knowledge ◽  
Insulin Signalling ◽  
Cell Signalling ◽  
Protein Tyrosine Phosphatases ◽  
Protein Tyrosine Kinases ◽  
Tyrosine Phosphatases ◽  
Large Protein ◽  
Protein Tyrosine ◽  
Wide Range

A cornerstone of many cell-signalling events rests on reversible phosphorylation of tyrosine residues on proteins. The reversibility relies on the coordinated actions of protein tyrosine kinases and protein tyrosine phosphatases (PTPs), both of which exist as large protein families. This review focuses on the rapidly evolving field of the PTPs. We now know that rather than simply scavenging phosphotyrosine, the PTPs specifically regulate a wide range of signalling pathways. To illustrate this and to highlight current areas of agreement and contention in the field, this review will present our understanding of PTP action in selected areas and will present current knowledge surrounding the regulatory mechanisms that control PTP enzymes themselves. It will be seen that PTPs control diverse processes such as focal adhesion dynamics, cell–cell adhesion and insulin signalling, and their own actions are in turn regulated by dimerisation, phosphorylation and reversible oxidation.

scholarly journals Protein-tyrosine Kinases Activate while Protein-tyrosine Phosphatases Inhibit L-type Calcium Channel Activity in Pituitary GH Cells

1996 ◽  
Vol 271 (16) ◽  
pp. 9441-9446 ◽  
Author(s):  
Mauro Cataldi ◽  
Maurizio Taglialatela ◽  
Salvatore Guerriero ◽  
Salvatore Amoroso ◽  
Gaetano Lombardi ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Tyrosine Kinases ◽  
Protein Tyrosine Phosphatases ◽  
Protein Tyrosine Kinases ◽  
Channel Activity ◽  
Tyrosine Phosphatases ◽  
Protein Tyrosine ◽  
Gh Cells

scholarly journals Protein Tyrosine Phosphatases: Mechanisms in Cancer

2021 ◽  
Vol 22 (23) ◽  
pp. 12865
Author(s):  
Vignesh Sivaganesh ◽  
Varsha Sivaganesh ◽  
Christina Scanlon ◽  
Alexander Iskander ◽  
Salma Maher ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Protein Tyrosine Phosphatases ◽  
Cancer Therapeutics ◽  
Protein Tyrosine Kinases ◽  
Tyrosine Phosphatases ◽  
Negative Regulators ◽  
Protein Tyrosine ◽  
Target Cancer

Protein tyrosine kinases, especially receptor tyrosine kinases, have dominated the cancer therapeutics sphere as proteins that can be inhibited to selectively target cancer. However, protein tyrosine phosphatases (PTPs) are also an emerging target. Though historically known as negative regulators of the oncogenic tyrosine kinases, PTPs are now known to be both tumor-suppressive and oncogenic. This review will highlight key protein tyrosine phosphatases that have been thoroughly investigated in various cancers. Furthermore, the different mechanisms underlying pro-cancerous and anti-cancerous PTPs will also be explored.

scholarly journals Functional interrogation and therapeutic targeting of protein tyrosine phosphatases

2021 ◽  
Author(s):  
Aaron D. Krabill ◽  
Zhong-Yin Zhang
Keyword(s):  
Enzymatic Activity ◽  
Tyrosine Kinases ◽  
Drug Target ◽  
Protein Tyrosine Phosphatases ◽  
Protein Tyrosine Kinases ◽  
Protein Tyrosine Phosphorylation ◽  
Tyrosine Phosphatases ◽  
Therapeutic Targeting ◽  
Protein Tyrosine ◽  
Disease States

Protein tyrosine phosphatases (PTPs) counteract the enzymatic activity of protein tyrosine kinases to modulate levels of both normal and disease-associated protein tyrosine phosphorylation. Aberrant activity of PTPs has been linked to the progression of many disease states, yet no PTP inhibitors are currently clinically available. PTPs are without a doubt a difficult drug target. Despite this, many selective, potent, and bioavailable PTP inhibitors have been described, suggesting PTPs should once again be looked at as viable therapeutic targets. Herein, we summarize recently discovered PTP inhibitors and their use in the functional interrogation of PTPs in disease states. In addition, an overview of the therapeutic targeting of PTPs is described using SHP2 as a representative target.

Roles of protein tyrosine phosphatases in cell migration and adhesion

1999 ◽  
Vol 77 (6) ◽  
pp. 493-505 ◽  
Author(s):  
Alexandre Angers-Loustau ◽  
Jean-François Côté ◽  
Michel L Tremblay
Keyword(s):  
Tyrosine Kinases ◽  
Protein Tyrosine Phosphatases ◽  
Cellular Migration ◽  
Tyrosine Phosphatases ◽  
Integrin Receptors ◽  
Protein Tyrosine ◽  
Kinase C ◽  
Cell Adhesion And Migration ◽  
And Migration ◽  
The Individual

Signal transduction pathways are often seen as cascades of kinases, whereas phosphatases are relinquished to the housekeeping function of resetting the individual elements to a resting state. However, critical biological processes such as cellular migration require a coordinated and constant remodeling of the actin cytoskeleton as well as a rapid turnover of the cell-substratum linkages that necessitate the concomitant action of antagonistic enzymes. Tyrosine phosphorylation was long known to be involved in adhesion and de-adhesion mediated via the integrin receptors. As the roles of tyrosine kinases such as focal adhesion kinase, c-Src, and Csk in this pathway are being extensively studied, increasing evidence is emerging about the importance of protein tyrosine phosphatases (PTP). In this review we discuss examples of PTPs that were recently shown to play a role in cell adhesion and migration and their mechanism of action.Key words: protein tyrosine phosphatases (PTP), migration, adhesion, FAK, p130Cas, Src.

scholarly journals A novel receptor-type protein tyrosine phosphatase with a single catalytic domain is specifically expressed in mouse brain

1995 ◽  
Vol 305 (2) ◽  
pp. 499-504 ◽  
Author(s):  
W Hendriks ◽  
J Schepens ◽  
C Brugman ◽  
P Zeeuwen ◽  
B Wieringa
Keyword(s):  
Mouse Brain ◽  
Tyrosine Kinases ◽  
Catalytic Domain ◽  
Tyrosine Phosphatase ◽  
Cell Signalling ◽  
Protein Tyrosine Phosphatases ◽  
Pcr Amplification ◽  
Phosphatase Domain ◽  
Protein Tyrosine ◽  
The Brain

Protein tyrosine phosphatases (PTPases) are important regulatory proteins that, together with protein tyrosine kinases, determine the phosphotyrosine levels in cell signalling proteins. By PCR amplification of mouse brain cDNA fragments encoding the catalytic domains of these enzymes, we identified three novel members of the PTPase gene family. Northern-blot analysis showed that two of these novel clones represent brain-specific PTPases, whereas the third originates from a large-sized mRNA that is more ubiquitously expressed. A full-length cDNA encoding one of the brain-specific PTPases, PTP-SL, was isolated. Sequence analysis revealed a transmembrane PTPase containing a single catalytic phosphatase domain that has 45% homology to a rat cytoplasmic brain-specific PTPase named STEP. This suggests a role for PTP-SL in cell-cell signalling processes in the brain.

Evolutionarily Conserved Allosteric Communication in Protein Tyrosine Phosphatases

2018 ◽  
Author(s):  
Michael K. Hjortness ◽  
Laura Riccardi ◽  
Akarawin Hongdusit ◽  
Peter H. Zwart ◽  
Banumathi Sankaran ◽  
...  
Keyword(s):  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatases ◽  
Kinetic Studies ◽  
Structural Basis ◽  
Tyrosine Phosphatases ◽  
Protein Tyrosine ◽  
Allosteric Communication ◽  
Wide Range ◽  
Evolutionarily Conserved ◽  
Dynamics Simulations

Protein tyrosine phosphatases (PTPs) are an important class of regulatory enzymes that exhibit aberrant activities in a wide range of diseases. A detailed mapping of allosteric communication in these enzymes could, thus, reveal the structural basis of physiologically relevant—and, perhaps, therapeutically informative—perturbations (i.e., mutations, post-translational modifications, or binding events) that influence their catalytic states. This study combines detailed biophysical studies of protein tyrosine phosphatase 1B (PTP1B) with bioinformatic analyses of the PTP family to examine allosteric communication in PTPs. Results of X-ray crystallography, molecular dynamics simulations, and sequence-based statistical analyses indicate that PTP1B possesses a broadly distributed allosteric network that is evolutionarily conserved across the PTP family, and findings from kinetic studies and mutational analyses show that this network is functionally intact in sequence-diverse PTPs. The allosteric network resolved in this study reveals new sites for targeting allosteric inhibitors of PTPs and helps explain the functional influence of a diverse set of disease-associated mutations.

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