Effects of heat shock on change of HSC70/HSP68,acid and alkaline phosphatases before and after rat partial hepatectomy

INTRODUCTIONOnly the liver has the great capability ofregeneration in mammal.Few hepatocytes are inthe phase of division in the normal liver of an adultmammal (including human beings),but theremaining hepatocytes can be induced to proliferatequickly by partial hepatectomy (PH),and,to somedegree,they stop dividing and re-differentiate intocells functioning as hepatocytes.This shows

Synthesis of tanshinoneⅡA analogues and their inhibitory activities against Cdc25 phosphatases

Two series of tanshinone ⅡA derivatives were synthesized and evaluated for their antitumor activities as Cdc25 phosphatase inhibitors. Most of them demonstrated potent Cdc25 inhibitory activity and powerful cytotoxicity against A549 tumor cell line, producing IC50 values in very low micromolar range. At last, the preliminary SAR was discussed.

Protein phosphatases and chromatin modifying complexes in the inflammatory cascade in acute pancreatitis

Acute pancreatitis is an inflammation of the pancreas that may lead to systemic inflammatory response syndrome and death due to multiple organ failure. Acinar cells, together with leukocytes, trigger the inflammatory cascade in response to local damage of the pancreas. Amplification of the inflammatory cascade requires up-regulation of proinflammatory cytokines and this process is mediated not only by nuclear factor κB but also by chromatinmodifying complexes and chromatin remodeling. Among the different families of histone acetyltransferases, the p300/CBP family seems to be particularly associated with the inflammatory process. cAMP activates gene expression via the cAMP-responsive element (CRE) and the transcription factor CRE-binding protein (CREB). CREB can be phosphorylated and activated by different kinases, such as protein kinase A and MAPK, and then it recruits the histone acetyltransferase co-activator CREB-binding protein (CBP) and its homologue p300. The recruitment of CBP/p300 and changes in the level of histone acetylation are required for transcription activation. Transcriptional repression is also a dynamic and essential mechanism of down-regulation of genes for resolution of inflammation, which seems to be mediated mainly by protein phosphatases (PP1, PP2A and MKP1) and histone deacetylases(HDACs) .Class HDACs are key transcriptional regulators whose activities are controlled via phosphorylationdependent nucleo/cytoplasmic shuttling. PP2A is responsible for dephosphorylation of class HDACs, triggeringnuclear localization and repression of target genes, whereas phosphorylation triggers cytoplasmic localization leading to activation of target genes. The potential benefit from treatment with phosphodiesterase inhibitors and histone deacetylase inhibitors is discussed.

Counter-regulatory phosphatases TNAP and NPP1 temporally regulate tooth root cementogenesis

Cementum is critical for anchoring the insertion of periodontal ligament fibers to the tooth root. Several aspects of cementogenesis remain unclear, including differences between acellular cementum and cellular cementum, and between cementum and bone. Biomineralization is regulated by the ratio of inorganic phosphate （Pi） to mineral inhibitor pyrophosphate （PPi）, where local Pi and PPi concentrations are controlled by phosphatases including tissue-nonspecific alkaline phosphatase （TNAP） and ectonucleotide pyrophosphatase/phosphodiesterase 1 （NPP1）. The focus of this study was to define the roles of these phosphatases in cementogenesis. TNAP was associated with earliest cementoblasts near forming acellular and cellular cementum. With loss of TNAP in the Alpl null mouse, acellular cementum was inhibited, while cellular cementum production increased, albeit as hypomineralized cementoid. In contrast, NPP1 was detected in cementoblasts after acellular cementum formation, and at low levels around cellular cementum. Loss of NPP1 in the Enppl null mouse increased acellular cementum, with little effect on cellular cementum. Developmental patterns were recapitulated in a mouse model for acellular cementum regeneration, with early TNAP expression and later NPP1 expression. In vitro, cementoblasts expressed Alpl gene/protein early, whereas Enppl gene/protein expression was significantly induced only under mineralization conditions. These patterns were confirmed in human teeth, including widespread TNAP, and NPP1 restricted to cementoblasts lining acellular cementum. These studies suggest that early TNAP expression creates a low PPi environment promoting acellular cementum initiation, while later NPP1 expression increases PPi, restricting acellular cementum apposition. Alterations in PPi have little effect on cellular cementum formation, though matrix mineralization is affected.

A description of alkaline phosphatases from marine organisms

Alkaline phosphatases(APs) are non-specifi c phosphohydrolases, and they are widely used in clinical diagnostics and biological studies. APs are widespread in nature and exhibit dif ferent structural formulations. Based on the diversity of biogenetic sources, APs exhibit temperature-propensity traits, and they are classifi ed as psychrophilic, mesophilic, and thermophilic. In this article, the characteristics of psychrophilic APs from marine organisms were described, accompanied by a simple description of APs from other organisms. This review will facilitate better utilization of marine APs in the biotechnology fi eld.

Metabolic regulation by protein tyrosine phosphatases

Obesity and the metabolic syndrome and their associated morbidities are major public health issues, whose prevalence will continue to increase in the foreseeable future. Aberrant signaling by the receptors for leptin and insulin plays a pivotal role in development of the metabolic syndrome. More complete molecular-level understanding of how both of these key signaling pathways are regulated is essential for full characterization of obesity, the metabolic syndrome, and type lI diabetes, and for developing novel treatments for these diseases. Phosphorylation of proteins on tyrosine residues plays a key role in mediating the effects of leptin and insulin on their target cells. Here, we discuss the molecular methods by which protein tyrosine phosphatases, which are key physiological regulators of protein phosphorylation in vivo, affect signaling by the leptin and insulin receptors in their major target tissues.

Mammalian-like Purple Acid Phosphatases in Plants

Introduction Purple acid phosphatases （PAPs） comprise of a family of binuclear metal-containing hydrolases, some members of which have been isolated and characterized from animal, plant and fungal sources . PAPs not only catalyze the hydrolyses of a wide range of phosphate esters and anhydrides under acidic reaction conditions, but also catalyze the generation of hydroxyl radicals in a Fenton-like reaction, by virtue of the presence of a redox-active binuclear metal center. Inmammals,

Functional repertoire of protein kinases and phosphatases in synaptic plasticity and associated neurological disorders

Protein phosphorylation and dephosphorylation are two essential and vital cellular mechanisms that regulate many receptors and enzymes through kinases and phosphatases.Ca^2+- dependent kinases and phosphatases are responsible for controlling neuronal processing;balance is achieved through opposition.During molecular mechanisms of learning and memory,kinases generally modulate positively while phosphatases modulate negatively.This review outlines some of the critical physiological and structural aspects of kinases and phosphatases involved in maintaining postsynaptic structural plasticity.It also explores the link between neuronal disorders and the deregulation of phosphatases and kinases.

Roles of protein tyrosine phosphatases in reproduction and related diseases

Protein tyrosine phosphatases(PTPs)remove phosphate groups from protein tyrosine residues to regulate various cell signaling processes,subsequently affecting the growth,metabolism,differentiation,immune response,and other cellular processes.Several studies have investigated the functions of PTPs in tumor and organism immunity.However,only a few studies have focused on their roles in reproductive disorders.Therefore,in this review,we summarize the roles and underlying molecular mechanisms of PTPs in infertility,spontaneous abortion,pregnancy-induced hypertension,gestational diabetes mellitus,early embryonic developmental abnormalities,and preterm birth.This review can contribute to future research on PTPs and their potential applications as targets in the treatment of reproductive diseases.

Recent progress on the structure of Ser/Thr protein phosphatases

PP1, PP2A and PP2B, belonging to the PPP family of Ser/Thr protein phosphatases, participate in regulating many important physiological processes, such as cell cycle control, regulation of cell growth and division regulation, etc. The sequence homology between them is relatively high, and ter- tiary structure is conserved. Because of the complexity of the structure of PP2A and the diversity of its regulatory subunits, its structure is less well known than those of PP1 and PP2B. The PP2A holoen- zyme consists of a heterodimeric core enzyme, comprising a scaffolding subunit and a catalytic sub- unit, as well as a variable regulatory subunit. In this study, the subunit compositions, similarities and differences between the Ser/Thr protein phsphatases structures are summarized.

Protein Tyrosine Phosphatases Mediate the Signaling Pathway of Stomatal Closure of Vicia faba L.

: The regulation of stomatal movement is one of the most important signaling networks in plants. The H+-ATPase at the plasma membrane of guard cells plays a critical role in the stomata opening, while there are some conflicting results regarding the effectiveness of the plasma membrane H+-ATPase inhibitor, vanadate, in inhibiting stomata opening. We observed that 2 mmol/L vanadate hardly inhibited light-stimulated stomata opening in epidermal peels of Vicia faba L., but significantly inhibited dark- and ABA-induced stomatal closure. These results cannot be explained with the previous findings that H+-ATPase was inhibited by vanadate. In view of the fact that vanadate is an inhibitor of protein tyrosine phosphatases (PTPases), we investigated whether the stomatal movement regulated by vanadate is through the regulation of PTPase. As expected, phenylarsine oxide (PAO), a specific inhibitor of PTPase, has very similar effects and even more effective than vanadate. Typical PTPase activity was found in guard cells of V. faba; moreover, the phosphatase activity could be inhibited by both vanadate and PAO. These results not only provide a novel explanation for conflicting results about vanadate modulating stomatal movement, but also provide further evidence for the involvement of PTPases in modulating signal transduction of stomatal movement.

Soybean(Glycine max)rhizosphere organic phosphorus recycling relies on acid phosphatase activity and specific phosphorusmineralizing-related bacteria in phosphate deficient acidic soils

Bacteria play critical roles in regulating soil phosphorus(P) cycling. The effects of interactions between crops and soil P-availability on bacterial communities and the feedback regulation of soil P cycling by the bacterial community modifications are poorly understood. Here, six soybean(Glycine max) genotypes with differences in P efficiency were cultivated in acidic soils with long-term sufficient or deficient P-fertilizer treatments. The acid phosphatase(AcP) activities, organic-P concentrations and associated bacterial community compositions were determined in bulk and rhizosphere soils. The results showed that both soybean plant P content and the soil AcP activity were negatively correlated with soil organic-P concentration in P-deficient acidic soils. Soil P-availability affected the ɑ-diversity of bacteria in both bulk and rhizosphere soils. However, soybean had a stronger effect on the bacterial community composition, as reflected by the similar biomarker bacteria in the rhizosphere soils in both P-treatments. The relative abundance of biomarker bacteria Proteobacteria was strongly correlated with soil organic-P concentration and AcP activity in low-P treatments. Further high-throughput sequencing of the phoC gene revealed an obvious shift in Proteobacteria groups between bulk soils and rhizosphere soils, which was emphasized by the higher relative abundances of Cupriavidus and Klebsiella, and lower relative abundance of Xanthomonas in rhizosphere soils. Among them, Cupriavidus was the dominant phoC bacterial genus, and it was negatively correlated with the soil organic-P concentration. These findings suggest that soybean growth relies on organic-P mineralization in P-deficient acidic soils, which might be partially achieved by recruiting specific phoCharboring bacteria, such as Cupriavidus.

Effects of phosphorus limitation on sinking velocities of phytoplankton during summer in the Changjiang River Estuary

The sinking of phytoplankton is critical to organic matter transportation in the ocean and it is an essential process for the formation of coastal hypoxic zones.This study was based on a field investigation conducted during the summer of 2022 in the Changjiang River(Yangtze River) Estuary(CJE) and its adjacent waters.The settling column method was employed to measure the sinking velocity(SV) of different size fractions of phytoplankton at the surface of the sea and to analyze their environmental control mechanisms.The findings reveal significant spatial variation in phytoplankton SV(-0.55-2.41 m/d) within the CJE.High-speed sinking was predominantly observed in phosphate-depleted regions beyond the CJE front.At the same time,an upward trend was more commonly observed in the phosphate-rich regions near the CJE mouth.The SV ranges for different sizefractionated phytoplankton,including micro-(>20 μm),nano-(2-20 μm),and picophytoplankton(0.7-2 μm),were-0.50-4.74 m/d,-1.04-1.59 m/d,and-1.24-1.65 m/d,respectively.Correlation analysis revealed a significant negative correlation between SV and dissolved inorganic phosphorus(DIP),implying that the influence of DIP contributes to SV.The variations in phytoplankton alkaline phosphatase activity suggested a significant increase in SV across all size fractions in the event of phosphorus limitation.Phytoplankton communities with limited photo synthetic capacity(maximum photochemical efficience,Fv/Fm <0.3) were found to have higher SV than that of communities with strong capacity,suggesting a link between sinking and alterations in physiological conditions due to phosphate depletion.The findings from the in situ phosphate enrichment experiments confirmed a marked decrease in SV following phosphate supplementation.These findings suggest that phosphorus limitation is the primary driver of elevated SV in the CJE.This study enhances the comprehension of the potential mechanisms underlying hypoxic zone formation in the CJE,providing novel insights into how nearshore eutrophication influences organic carbon migration.

Inhibiting SHP2 reduces glycolysis, promotes microglial M1 polarization, and alleviates secondary inflammation following spinal cord injury in a mouse model

Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2(SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury.

Pachymic acid exerts antitumor activities by modulating the Wnt/β-catenin signaling pathway via targeting PTP1B

Objective:To determine the inhibitory effects of pachymic acid on lung adenocarcinoma(LUAD)cells and elucidate its underlying mechanism.Methods:CCK-8,wound healing,Transwell,Western blot,tube formation,and immunofluorescence assays were carried out to measure the effects of various concentrations of pachymic acid on LUAD cell proliferation,metastasis,angiogenesis as well as autophagy.Subsequently,molecular docking technology was used to detect the potential targeted binding association between pachymic acid and protein tyrosine phosphatase 1B(PTP1B).Moreover,PTP1B was overexpressed in A549 cells to detect the specific mechanisms of pachymic acid.Results:Pachymic acid suppressed LUAD cell viability,metastasis as well as angiogenesis while inducing cell autophagy.It also targeted PTP1B and lowered PTP1B expression.However,PTP1B overexpression reversed the effects of pachymic acid on metastasis,angiogenesis,and autophagy as well as the expression of Wnt3a andβ-catenin in LUAD cells.Conclusions:Pachymic acid inhibits metastasis and angiogenesis,and promotes autophagy in LUAD cells by modulating the Wnt/β-catenin signaling pathway via targeting PTP1B.

Protein tyrosine phosphatase non-receptor Ⅱ:A possible biomarker of poor prognosis and mediator of immune evasion in hepatocellular carcinoma

BACKGROUND The incidence of primary liver cancer is increasing year by year.In 2022 alone,more than 900000 people were diagnosed with liver cancer worldwide,with hepatocellular carcinoma(HCC)accounting for 75%-85%of cases.HCC is the most common primary liver cancer.China has the highest incidence and mortality rate of HCC in the world,and it is one of the malignant tumors that seriously threaten the health of Chinese people.The onset of liver cancer is occult,the early cases lack typical clinical symptoms,and most of the patients are already in the middle and late stage when diagnosed.Therefore,it is very important to find new markers for the early detection and diagnosis of liver cancer,improve the therapeutic effect,and improve the prognosis of patients.Protein tyrosine phosphatase non-receptor 2(PTPN2)has been shown to be associated with colorectal cancer,triple-negative breast cancer,non-small cell lung cancer,and prostate cancer,but its biological role and function in tumors remain to be further studied.AIM To combine the results of relevant data obtained from The Cancer Genome Atlas(TCGA)to provide the first in-depth analysis of the biological role of PTPN2 in HCC.METHODS The expression of PTPN2 in HCC was first analyzed based on the TCGA database,and the findings were then verified by immunohistochemical staining,quantitative real-time polymerase chain reaction(qRT-PCR),and immunoblotting.The value of PTPN2 in predicting the survival of patients with HCC was assessed by analyzing the relationship between PTPN2 expression in HCC tissues and clinicopathological features.Finally,the potential of PTPN2 affecting immune escape of liver cancer was evaluated by tumor immune dysfunction and exclusion and immunohistochemical staining.RESULTS The results of immunohistochemical staining,qRT-PCR,and immunoblotting in combination with TCGA database analysis showed that PTPN2 was highly expressed and associated with a poor prognosis in HCC patients.Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that PTPN2 was associated with various pathways,including cancer-related pathways,the Notch signaling pathway,and the MAPK signaling pathway.Gene Set Enrichment Analysis showed that PTPN2 was highly expressed in various immune-related pathways,such as the epithelial mesenchymal transition process.A risk model score based on PTPN2 showed that immune escape was significantly enhanced in the high-risk group compared with the low-risk group.CONCLUSION This study investigated PTPN2 from multiple biological perspectives,revealing that PTPN2 can function as a biomarker of poor prognosis and mediate immune evasion in HCC.

Bioactive chemical constituents from the marine-derived fungus Cladosporium sp.DLT-5

A new isochromanone,cladosporinisochromanone(1),accompanied by 15 known compounds(2–16)were obtained from secondary metabolites produced by marine-derived fungus Cladosporium sp.DLT-5.NMR and HRESIMS spectra elucidation determined the planar structure of 1.Subsequent electronic circular dichroism(ECD)experiment assigned the absolute configuration of 1.Compounds 1,2,4–6,and 10 displayed different degrees of neuroprotective activities on human neuroblastoma cells SH-SY5Y.Five compounds(1,3–5,and 13)emerged resistance to protein tyrosine phosphatase 1B(PTP1B),further kinetic analysis and molecular docking study indicated that the most potent compound 13(IC50value of 10.74±0.61μmol/L)was found as a noncompetitive inhibitor for PTP1B.Surface plasmon resonance(SPR)and molecular docking studies also demonstrated the interaction between compound 12 and Niemann-Pick C1 Like 1(NPC1L1),which has been identified as significant therapeutic target for hypercholesteremia.In addition,compounds 3,6,and 14 showed attractive inhibitory activity against the phytopathogenic fungi:Colletotrichum capsici.Therefore,library of Cladosporium metabolites is enriched and new active uses of known compounds are explored.

Analysis of alkaline phosphatase and γ-glutamyltransferase after radiofrequency ablation of primary liver cancer: A retrospective study

BACKGROUND Changes in alkaline phosphatase(ALP)andγ-glutamyltransferase(GGT)levels in patients with primary liver cancer(PLC)after radiofrequency ablation(RFA).Hepatocellular carcinoma is a malignant tumor with high incidence worldwide.As a common local treatment,RFA has attracted much attention for its efficacy and influence on liver function.AIM To investigate the effect of serum ALP and GGT levels on the prognosis of patients with PLC treated by RFA.METHODS The preoperative clinical data of 165 patients who were pathologically or clinically diagnosed with PLC and who received RFA in our hospital between October 2018 and June 2023 were collected.The chi-square test was used to compare the data between groups.The Kaplan-Meier method and Cox regression were used to analyze the associ-ations between serum ALP and GGT levels and overall survival,progression-free survival(PFS)and clinical characteristics of patients before treatment.RESULTS The 1-year survival rates of patients with normal(≤135 U/L)and abnormal(>135 U/L)serum ALP before treatment were 91%and 79%,respectively;the 2-year survival rates were 90%and 68%,respectively;and the 5-year survival rates were 35%and 18%,respectively.The difference between the two groups was statistically significant(P=0.01).Before treatment,the 1-year survival rates of patients with normal serum GGT levels(≤45 U/L)and abnormal serum GGT levels(>45 U/L)were 95%and 87%,the 2-year survival rates were 85%and 71%,and the 5-year survival rates were 37%and 21%,respectively.The difference between the two groups was statist-ically significant(P<0.001).Serum ALP[hazard ratio(HR)=1.766,95%confidence interval(95%CI):1.068-2.921,P=0.027]and GGT(HR=2.312,95%CI:1.367-3.912,P=0.002)is closely related to the overall survival of PLC patients after RF ablation and is an independent prognostic factor.The 1-year PFS rates were 72%and 50%,the 2-year PFS rates were 52%and 21%,and the 5-year PFS rates were 14%and 3%,respectively.The difference between the two groups was statistically significant(P<0001).The 1-year PFS rates were 81%and 56%in patients with normal and abnormal serum GGT levels before treatment,respectively;the 2-year PFS rates were 62%and 35%,respectively;and the 5-year PFS rates were 18%and 7%,respectively,with statistical significance between the two groups(P<0.001).The serum ALP concentration(HR=1.653,95%CI:1.001-2.729,P=0.049)and GGT(HR=1.949,95%CI:1.296-2.930,P=0.001)was closely associated with PFS after RFA in patients with PLC.The proportion of male patients with abnormal ALP levels is high,the Child-Pugh grade of liver function is poor,and the incidence of ascites is high.Among GGT-abnormal patients,the Child-Pugh grade of liver function was poor,the tumor stage was late,the proportion of patients with tumors≥5 cm was high,and the incidence of hepatic encephalopathy was high.CONCLUSION Serum ALP and GGT levels before treatment can be used to predict the prognosis of patients with PLC after RFA,and they have certain guiding significance for the long-term survival of patients with PLC after radiofrequency therapy.

Hepatoprotective effects of Xiaoyao San formula on hepatic steatosis and inflammation via regulating the sex hormones metabolism

BACKGROUND The modified Xiaoyao San(MXS)formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer,which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient survival.However,the molecular mechanisms underlying that remain unclear.AIM To investigate the role and mechanisms of MXS in ameliorating hepatic injury,steatosis and inflammation.METHODS A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis(NASH)model was used to examine the effects of MXS on lipid accumulation in primary hepatocytes.Liver tissues were collected for western blotting and immunohisto chemistry(IHC)assays.Lipid accumulation and hepatic fibrosis were detected using oil red staining and Sirius red staining.The serum samples were collected for biochemical assays and NMR-based metabonomics analysis.The inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against NASH.RESULTS MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress.The western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation,inflammation and hepatic fibrosis in the pathogenesis of NASH.The metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic steatosis.Mechanistically,we found that MXS protected against NASH by attenuating the sex hormone-related metabolism,especially the metabolism of male hormones.CONCLUSION MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male hormones.Targeting male hormone related metabolic pathways may be the potential therapeutic approach for NASH.

Phosphatases of regenerating liver： a novel target in human solid tumors

Protein tyrosine phosphorylation is a major posttranslational modification used by cells to regulate signal transduction and essentially participate in every aspect of cellular physiologic and pathogenic processes. The protein tyrosine phosphatase （PTP） super family of enzymes coordinately function with protein tyrosine kinases in signaling pathways that underlie a broad spectrum of fundamental physiological processes. Abnormal regulation of tyrosine phosphorylation or deregulation of phosphorylation is known to result in neoplastic or non-neoplastic diseases. Having evolved into separate families that are structurally and mechanistically distinct, PTPs have been implicated in a variety of diseases and efforts have been made to seek therapeutic clues from them. The phosphatases of regenerating liver （PRL） PRL-1, PRL-2, PRL-3 （also known as PTP4A1, PTP4A2, and PTP4A3, respectively） constitute a subfamily of the protein tyrosine phosphatases that have been suggested to play a key role in oncogenic and metastatic phenotypes.5 Here we review what is known about this novel class of small, prenylated phosphatases and its value in diagnosis and therapy of solid tumors.