Protein tyrosine phosphatases: prospects for therapeutics

Zhang, Zhong-Yin

doi:10.1016/s1367-5931(00)00223-4

Cited by 342 publications

(205 citation statements)

References 60 publications

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“…This family of enzymes consists of key factors in a variety of cellular processes including cell growth, differentiation, 15 Malfunction of PTP activity is associated with a number of human disorders, including cancers, diabetes, rheumatoid arthritis and hypertension. 16 Studies of PTPRR-deficient mice showed that PTPRR isoforms 17 are physiological regulators of MAPK phosphorylation. These mice displayed impaired motor coordination and defects in their balance skills, reminiscent of a mild ataxia because of altered MAPK signaling.…”

Section: Discussionmentioning

confidence: 99%

Nasal speech and hypothyroidism are common hallmarks of 12q15 microdeletions

et al. 2011

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The introduction of array CGH in clinical diagnostics has led to the discovery of many new microdeletion/microduplication syndromes. Most of them are rare and often present with a variable range of clinical anomalies. In this study we report three patients with a de novo overlapping microdeletion of chromosome bands 12q15q21.1. The deletions are similar to 2.5Mb in size, with a 1.34-Mb common deleted region containing six RefSeq genes. All three patients present with learning disability or developmental delay, nasal speech and hypothyroidism. In this paper we will further elaborate on the genotype-phenotype correlation associated with this deletion and compare our patients with previously reported cases

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Section: Discussionmentioning

confidence: 99%

Nasal speech and hypothyroidism are common hallmarks of 12q15 microdeletions

et al. 2011

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“…Finally, there is growing interest in the potential of phosphatases as drug targets in various diseases, including diabetes, obesity, and cancer (45)(46)(47). In cancer, two recent reports have highlighted the role of the PTP1B phosphatase, encoded by a gene in the 20q13 region, which is also amplified in breast cancer, in ERBB2-induced mammary tumorigenesis (7,8).…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Recurrent 8p11-12 Amplicon Identifies PPAPDC1B, a Phosphatase Protein, as a New Therapeutic Target in Breast Cancer

et al. 2008

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The 8p11-12 chromosome region is one of the regions most frequently amplified in breast carcinoma (10-15% of cases). Several genes within this region have been identified as candidate oncogenes, as they are both amplified and overexpressed. However, very few studies have explored the role of these genes in cell transformation, with the aim of identifying valuable therapeutic targets. An analysis of comparative genomic hybridization array and expression profiling data for a series of 152 ductal breast carcinomas and 21 cell lines identified five genes (LSM1, BAG4, DDHD2, PPAPDC1B, and WHSC1L1) within the amplified region as consistently overexpressed due to an increased gene copy number. The use of small interfering RNA to knock down the expression of each of these genes showed the major role played by two genes, PPAPDC1B and WHSC1L1, in regulating the survival and transformation of two different cell lines harboring the 8p amplicon. The role of these two genes in cell survival and cell transformation was also confirmed by long-term knockdown expression studies using short hairpin RNAs. The potential of PPAPDC1B, which encodes a transmembrane phosphatase, as a therapeutic target was further shown by the strong inhibition of growth of breast tumor xenografts displaying 8p11-12 amplification induced by the silencing of PPAPDC1B. The oncogenic properties of PPAPDC1B were further shown by its ability to transform NIH-3T3 fibroblasts, inducing their anchorage-independent growth. Finally, microarray experiments on PPAPDC1B knockdown indicated that this gene interfered with multiple cell signaling pathways, including the Janus-activated kinase-signal transducer and activator of transcription, mitogen-activated protein kinase, and protein kinase C pathways. PPAPDC1B may also potentiate the estrogen receptor pathway by downregulating DUSP22. [Cancer Res 2008;68(17):7165-75]

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“…Malfunction of PTP activity has been linked to cancer, diabetes, and immune dysfunctions (3). The importance of PTPs in cellular physiology is further underscored by the fact that they are often exploited and subverted by pathogenic bacteria to cause human diseases.…”

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confidence: 99%

Targeting mycobacterium protein tyrosine phosphatase B for antituberculosis agents

Zhou¹,

He²,

Zhang

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Protein tyrosine phosphatases are often exploited and subverted by pathogenic bacteria to cause human diseases. The tyrosine phosphatase mPTPB from Mycobacterium tuberculosis is an essential virulence factor that is secreted by the bacterium into the cytoplasm of macrophages, where it mediates mycobacterial survival in the host. Consequently, there is considerable interest in understanding the mechanism by which mPTPB evades the host immune responses, and in developing potent and selective mPTPB inhibitors as unique antituberculosis (antiTB) agents. We uncovered that mPTPB subverts the innate immune responses by blocking the ERK1/2 and p38 mediated IL-6 production and promoting host cell survival by activating the Akt pathway. We identified a potent and selective mPTPB inhibitor I-A09 with highly efficacious cellular activity, from a combinatorial library of bidentate benzofuran salicylic acid derivatives assembled by click chemistry. We demonstrated that inhibition of mPTPB with I-A09 in macrophages reverses the altered host immune responses induced by the bacterial phosphatase and prevents TB growth in host cells. The results provide the necessary proof-of-principle data to support the notion that specific inhibitors of the mPTPB may serve as effective antiTB therapeutics.combinatorial chemistry | pathogen-host interaction | phosphatase inhibitor | signaling mechanism

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Protein tyrosine phosphatases: prospects for therapeutics

Cited by 342 publications

References 60 publications

Nasal speech and hypothyroidism are common hallmarks of 12q15 microdeletions

Nasal speech and hypothyroidism are common hallmarks of 12q15 microdeletions

Characterization of the Recurrent 8p11-12 Amplicon Identifies PPAPDC1B, a Phosphatase Protein, as a New Therapeutic Target in Breast Cancer

Targeting mycobacterium protein tyrosine phosphatase B for antituberculosis agents

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