Low molecular weight protein tyrosine phosphatase: Multifaceted functions of an evolutionarily conserved enzyme

Caselli, Anna; Paoli, Paolo; Santi, Alice; Mugnaioni, Camilla; Toti, Alessandra; Camici, Giovanni G.; Cirri, Paolo

doi:10.1016/j.bbapap.2016.07.001

Cited by 40 publications

(46 citation statements)

References 157 publications

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“…The α-sulfophenylacetic amide (SPAA) pharmacophore from Cefsulodin, a β-lactam antibiotic that inhibits several PTPs, inspired generation of selective competitive inhibitors of low-molecular weight PTP (LMPTP or LMW-PTP)[15], an inhibitor of insulin receptor (IR) phosphorylation[16]. Compound 28 was identified from a library generated by reacting α-sulfophenylacetic acid with varying amines, followed by structure-guided medicinal chemistry[15].…”

Section: Trends In Small-molecule Ptp Inhibitor Developmentmentioning

confidence: 99%

Targeting Tyrosine Phosphatases: Time to End the Stigma

Stanford

Bottini

2017

Trends in Pharmacological Sciences

156

147

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Protein tyrosine phosphatases (PTPs) are a family of enzymes essential for numerous cellular processes, and several PTPs have been validated as therapeutic targets for human diseases. Historically, development of drugs targeting PTPs has been highly challenging, leading to stigmatization of these enzymes as undruggable targets. Despite these difficulties, efforts to drug PTPs have persisted, and recent years have seen an influx of new probes, providing opportunities for biological examination of old and new PTP targets. Here we will discuss progress towards drugging PTPs, with special emphasis on development of selective probes with biological activity. We will describe development of new small-molecule orthosteric, allosteric and oligomerization PTP inhibitors, and discuss new studies targeting the receptor PTP subfamily with biologics.

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Section: Trends In Small-molecule Ptp Inhibitor Developmentmentioning

confidence: 99%

Targeting Tyrosine Phosphatases: Time to End the Stigma

Stanford

Bottini

2017

Trends in Pharmacological Sciences

156

147

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“…LMW-PTP activities are regulated through cysteine oxidation and tyrosine phosphorylation [5]; LMW-PTP is involved in carcinogenesis of various cancers [7]. Recently, we reported LMW-PTP to be a possible predictive factor for overall survival among men with mHNPC [8].…”

Section: Prediction Of Time To Castration-resistantmentioning

confidence: 99%

“…Low-molecular-weight protein tyrosine phosphatase (LMW-PTP) is an 18-kDa protein tyrosine phosphatase DOI: 10.1159/000493324 that acts on many phosphotyrosine-containing cellular proteins that primarily affect signal transduction [5,6]. LMW-PTP activities are regulated through cysteine oxidation and tyrosine phosphorylation [5]; LMW-PTP is involved in carcinogenesis of various cancers [7].…”

Section: Prediction Of Time To Castration-resistantmentioning

confidence: 99%

Prediction of Time to Castration-Resistant Prostate Cancer Using Low-Molecular-Weight Protein Tyrosine Phosphatase Expression for Men with Metastatic Hormone-Naïve Prostate Cancer

et al. 2018

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Introduction: Low-molecular-weight protein tyrosine phosphatase (LMW-PTP) expression affects carcinogenesis in various cancers and has been associated with determining the overall survival among men with metastatic hormone-naïve prostate cancer (mHNPC). In this study, we analyzed the value of LMWPTP for prediction of time to castration-resistant prostate cancer (CRPC) for men with mHNPC. Materials and Methods: We retrospectively enrolled 45 men with mHNPC who were diagnosed from 2003 to 2009. All patients had received androgen deprivation therapy as first-line treatment. Prostate cancer tissues (pre-treatment needle biopsies) were immunohistochemically stained for LMW-PTP. Multivariate analyses (Cox proportional hazard model) were used to correlate baseline clinical factors of age, prostate-specific antigen (PSA), Gleason scores, T stage, N stage, extent of disease on bone scan (EOD), LMW-PTP expression and time to CRPC. Continuous variables were classified as dichotomous. Results: Median age and PSA were 70.0 years and 87.8 ng/mL respectively. Median time to CRPC was 40.2 months. Median time to CRPC was significantly shorter in the high LMW-PTP group (14.8 months) than that in the low LMW-PTP group (86.3 months, p < 0.01). In multivariate analysis, age ≥70 years and high LMW-PTP expression were significant predictors of time to CRPC.

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“…In particular, their involvement in the synthesis and export of polysaccharides responsible for biofilm and capsule formation, antibiotic resistance, lysogenization and DNA metabolism has been demonstrated. PTPs can be divided into three families: high-molecular-weight PTPs (HMW-PTPs; receptor-like and nonreceptor), dual-specificity PTPs (DS-PTPs; specificity for phospho-tyrosine and phospho-serine/ threonine) and low-molecular-weight PTPs (LMW-PTPs), with a molecular mass of about 18 kDa (Walton & Dixon, 1993;Charbonneau & Tonks, 1992;Tabernero et al, 2008;Blenis, 1993;Yuvaniyama et al, 1996;Zhang et al, 1995;Raugei et al, 2002;Caselli et al, 2016). The three PTP families share no sequence homology apart from a signature motif C(X) 5 R(S/T) contributing to the phosphate-binding loop (P-loop) in the active site and a catalytic aspartate residue followed by a proline and often a tyrosine, which are part of the so-called D-loop.…”

Section: Introductionmentioning

confidence: 99%

Characterization and 1.57 Å resolution structure of the key fire blight phosphatase AmsI fromErwinia amylovora

2016

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AmsI is a low-molecular-weight protein tyrosine phosphatase that regulates the production of amylovoran in the Gram-negative bacterium Erwinia amylovora, a specific pathogen of rosaceous plants such as apple, pear and quince. Amylovoran is an exopolysaccharide that is necessary for successful infection. In order to shed light on AmsI, its structure was solved at 1.57 Å resolution at the same pH as its highest measured activity (pH 5.5). In the active site, a water molecule, bridging between the catalytic Arg15 and the reaction-product analogue sulfate, might be representative of the water molecule attacking the phospho-cysteine intermediate in the second step of the reaction mechanism.

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Low molecular weight protein tyrosine phosphatase: Multifaceted functions of an evolutionarily conserved enzyme

Cited by 40 publications

References 157 publications

Targeting Tyrosine Phosphatases: Time to End the Stigma

Targeting Tyrosine Phosphatases: Time to End the Stigma

Prediction of Time to Castration-Resistant Prostate Cancer Using Low-Molecular-Weight Protein Tyrosine Phosphatase Expression for Men with Metastatic Hormone-Naïve Prostate Cancer

Characterization and 1.57 Å resolution structure of the key fire blight phosphatase AmsI fromErwinia amylovora

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