The phosphorylation and dephosphorylation of signaling molecules play a crucial role in various cellular processes, including immune responses. As a result of their essential role in regulating protein tyrosine phosphorylation levels, protein tyrosine phosphatases ptps have emerged as important yet challenging therapeutic targets. Pdf mining the function of protein tyrosine phosphatases. Interestingly, both loss offunction and gainoffunction mutations in these genes may underlie the reported disease. Role of protein tyrosine phosphatases in cancer signaling. Mining the function of protein tyrosine phosphatases in health and disease article pdf available in seminars in cell and developmental biology 37 september 2014 with 577 reads.
Historically, the development of drugs targeting eral. Protein tyrosine phosphatases in health and disease. Protection of epithelial barrier function by the crohns. Protein tyrosine phosphatases ptp are a family of enzymes that hydrolytically remove phosphate groups from proteins. Proteinphosphatases that dephosphorylate either tyrosine or serine and threonine constitute the two main families and are referred to as protein tyrosine phosphatases ptps and protein serinethreonine phosphatases pps, respectively. Mining the function of protein tyrosine phosphatases in. Protein phosphorylation and dephosphorylation are complex enzymatic reactions that are performed by the concerted action of protein kinases and phosphatases, respectively. Protein tyrosine phosphatases ptps catalyse removal, and protein tyrosine kinases ptks the addition of phosphate. Using genomic data on protein phosphatases across eukaryotic animal kingdoms, chen et al. Overall, there are approximately 100 human ptpsuperfamily genes, compared to 90 human protein tyrosine kinase ptk genes, suggesting similar levels of. Several ptps, ptpn22, ptpn2, and ubash3a, have been associated with risk of type 1 diabetes t1d by. Review article protein tyrosine phosphatases in health and.
Protein tyrosine phosphatases can no longer be viewed as passive housekeeping enzymes. Targeting protein tyrosine phosphatases in cancer lakshmi reddy bollu, abhijit mazumdar, michelle i. Dysregulation of protein tyrosine phosphorylation has been implicated in a number of human diseases, including cancer, diabetes, and neurodegenerative diseases. Protein tyrosine kinases and protein tyrosine phosphatases. Review protein kinases, their function and implication in. The protein tyrosine phosphatase ptp superfamily of enzymes functions in a coordinated manner with protein tyrosine kinases to control signalling pathways that underlie a broad spectrum of fundamental physiological processes.
Loss of heterozygosity of the human gene was noted in 19 out of 39 colorectal adenocarcinomas ruivenkamp et al. Protein tyrosine phosphorylation is a fundamental mechanism for numerous physiologically important phenomena, such as cellular activation, proliferation, differentiation, migration, homeostasis, and death, and is strictly controlled by protein tyrosine kinases ptks and protein tyrosine phosphatases ptps 1, 2. Identification of protein tyrosine phosphatase 1b ptp1b. Deregulation of such coordination due to loss or gain of a single component of the process can result in. In response to extracellular signals, protein kinases activate downstream signaling pathways through a series of protein phosphorylation events, ultimately producing a signal response. Review article protein tyrosine phosphatases in health and disease wiljan j.
Protein tyrosine phosphatase an overview sciencedirect. Systematic global analysis of genes encoding protein phosphatases in aspergillus fumigatus. Expression of proteintyrosine phosphatases in acute. Brown abstract the aberrant activation of oncogenic signaling pathways is a universal phenomenon in cancer and drives tumorigenesis and malignant transformation. Tyr phosphorylated proteins have been detected in higher plants, and the roles of protein tyr phosphatases and protein tyr kinases in some physiological responses have been shown. Physiological signaling specificity by protein tyrosine. The four families of ptpases, their substrates, structure, function, regulation, and the role of these enzymes in human disease will be. Dixon given the importance of tyrosine phosphorylation of proteins in signalling pathways, it is perhaps not surprising that protein o,rosine phosphatases ptps ae involved in the patho, genesis of certain human diseases.
Protein tyrosine ptyr phosphorylation is a common posttranslational modification that can create novel recognition motifs for protein interactions and cellular localization, affect protein stability, and regulate enzyme activity. Tyrosine phosphorylation is catalyzed by protein tyrosine kinases, which are. Protein tyrosine phosphorylation is a key regulatory mechanism in eukaryotic cell physiology. Protein tyrosine phosphatases in health and disease wiley online.
Therapeutic targeting of oncogenic tyrosine phosphatases. Stanford1 and nunzio bottini1, 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. Dusps possess the capability to dephosphorylate serthr and tyr residues from proteins as well as to remove phosphates from other nonproteinaceous substrates, including. Genomics and evolution of protein phosphatases science. The ptpn22 gene provides instructions for making a protein that belongs to the ptp protein tyrosine phosphatases family. Protein tyrosine phosphatases ptps play a crucial role in the regulation of human health and it is now clear that ptp dysfunction is causal to a variety of human diseases. This study has provided important foundations for understanding kinase sig. Protein tyrosine phosphatases ptps are a large family of enzymes that generally oppose the actions of protein tyrosine kinases ptks. From ncbi gene the protein encoded by this gene is a member of the protein tyrosine phosphatase ptp family. Protein tyrosine phosphatases and inflammatory disease macrophages are possibly the most important inflammatory cell type to be aberrantly activated in chronic inflammatory diseases such as rheumatoid arthritis, but little is known about intracellular regulation of ptps in these cells. Protein tyrosine tyr phosphorylation plays a central role in many signaling pathways leading to cell growth and differentiation in animals. Protein tyrosine phosphatases and cancer sanne rijnders university of utrecht. Of these, 81 genes are catalytically active and dephosphorylate tyrosine residues, whereas the majority of the remainder are inactive or dephosphorylate inositol phospholipids 1. Protein tyrosine phosphatases are a group of enzymes that remove phosphate groups from phosphorylated tyrosine residues on proteins.
A lot of ptps can function either as positive or negative modulators in a variety of signal transduction pathways. Protein tyrosine phosphatase an overview sciencedirect topics. With the refdic reference genomics database of immune cells database compiled by riken rikagaku kenkyusho. Protein tyrosine phosphatase 1b ptp1b, the first purified ptp, is a widely expressed 50 kda enzyme and localized mainly in the endoplasmic reticulum. Negative regulation of receptor tyrosine kinases by tcell. Tyrosine phosphorylation is a fundamental mechanism for numerous important aspects of eukaryote physiology, as well as human health and disease hunter 1987, mustelin et al. In signal transduction, the protein relays signals from outside the cell to the cell nucleus. Dual specificity phosphatases dusps constitute a heterogeneous group of enzymes, relevant in human disease, which belong to the class i cysbased group of protein tyrosine phosphatase ptp gene superfamily 1,2,3,4. Here, we present the set of 107 genes in the human genome that encode members of the four protein tyrosine phosphatase ptp families. Studying protein tyrosine phosphatases in zebrafish. Proteintyrosine phosphatases ptp are important regulators of cellular signal transduction. Systematic global analysis of genes encoding protein.
Download citation tonks nk protein tyrosine phosphatases. Aberrant expression or function of protein tyrosine kinases and protein tyrosine phosphatases can lead. Protein tyrosine phosphatases ptps catalyze the dephosphorylation of phosphotyrosine, a key reaction for the control of mammalian signal transduction 1. A protein phosphatase is a phosphatase enzyme that removes a phosphate group from the phosphorylated amino acid residue of its substrate protein. Later, genome analysis revealed that one of the mouse genes for susceptibility to colorectal cancer encodes a receptor tyrosine phosphatase, ptprj. Tyrosine phosphorylation is catalyzed by protein tyrosine kinases, which are represented by 90 genes in the human genome. Genetics and biochemical studies indicate that ptps are involved in a number of disease processes. The generation of animal model systems and the study of various human disease states have begun to elucidate the important and diverse roles of protein tyrosine phosphatases in cellular signalling pathways, development and disease. Protein tyrosine phosphatases in disease processes elizabeth g. Genetic polymorphisms for particular ptps are associated with altered risk of both type 1 diabetes t1d and type 2 diabetes t2d.
There are 107 protein tyrosine phosphatases ptps in the human genome and many of these play important roles in cellular function. In spite of the large number of ptps identified to date, and the. Protein tyrosine phosphatases ptps represent a superfamily of enzymes that play essential roles in normal development and physiology. Protein phosphorylation is involved in various diseases, including. Ptps constitute the largest family of phosphatase genes and are. With 107 members, the ptp gene family is one of the most diverse in the mammalian genome.
Ptp proteins play a role in regulating a process called signal transduction. The results of this work are a list table 1 of all genes in the human genome. To date, the global expression profile of protein tyrosine phosphatases ptps in various immune cells has not been described. Protein tyrosine phosphatases in health and disease hendriks. Protein tyrosine phosphatases in the human genome sciencedirect. Tonks abstract the protein tyrosine phosphatase ptp superfamily of enzymes functions in a coordinated manner with protein tyrosine kinases to control signalling pathways that underlie a broad spectrum of fundamental physiological processes. Protein tyrosine phosphatases, new targets for cancer. Protein tyrosyl phosphorylation is fundamental to the maintenance of numerous cellular functions including gene expression, cell growth, differentiation, migration, adhesion and apoptosis. Because protein tyrosine phosphorylation is a dynamic and reversible posttranslational modification that is orchestrated by a regulatory partnership between ptks and protein tyrosine phosphatases ptp, there is the potential to modulate disease progression by targeting the ptps.
Aberrant expression or function of protein tyrosine kinases and protein tyrosine phosphatases can lead to serious human diseases, including cancer, diabetes, as well as cardiovascular, infectious, autoimmune, and neuropsychiatric disorders. Comprehensive expression profiles of genes for protein. Striatalenriched protein tyrosine phosphatase step, encoded by the ptpn5 gene, is a cnsenriched member of the ptp family. Relative to kinases, protein phosphatases are more structurally and catalytically diverse. They also tabulated disease associations with various human phosphatases. Compared to protein phosphorylation in general, phosphorylation on tyrosine is extensively utilized only in multicellular eukaryotes. Pdf protein tyrosine phosphatases in health and disease. Protein tyrosine phosphatases ptps are a large family of signal transduction regulators that have an essential role in normal development and physiology. To gain a deeper insight into the function of the identified phosphatases.
Ptps are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. Since protein tyrosine phosphorylation is a dynamic and reversible posttranslational modification that is orchestrated by a regulatory partnership between ptks and protein tyrosine phosphatases ptps, there is the potential to modulate disease progression by targeting the ptps. The net level of cellular protein tyrosyl phosphorylation is balanced by the opposing actions of both protein tyrosine kinases ptks and protein tyrosine phosphatases ptps. Protein phosphorylation is one of the most common forms of reversible protein posttranslational modification, with up to 30% of all proteins being phosphorylated at any given time. Moreover, recent evidence suggests that ptps play crucial roles in metabolism. Several types of alterations of specific ptp functions have been reported in cancer cells, including gene deletion, allele loss, reduced expression by promoter methylation, or inactivation by point mutation or oxidation, all leading to lossof function 1, 2. Protein tyrosine phosphatases ptps constitute a large family of enzymes that can exert both positive and negative effects on signaling pathways. Role of striatalenriched tyrosine phosphatase in neuronal. Ptprj is the first tyrosine specific ptp to be assigned a convincing role as. Protein tyrosine phosphatases ptps play a central role in modulating the transduction of cellular signals, including the cells of the immune system. It is now becoming apparent that they have important roles in the regulation of signalling responses. Data from various sources support a role for ptks in transformation and it has long been hypothesized that some ptps will function as tumour suppressor genes.
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