Structure of human PRL‐3, the phosphatase associated with cancer metastasis

Kim, Kyoung Ah; Song, Jin Sue; Jee, Jun Goo; Sheen, Mee Rie; Lee, Chulhyun; Lee, Tae Gyu; Ro, Seonggu; Cho, Joong Myung; Lee, Weontae; Yamazaki, Toshio; Jeon, Young Ho; Cheong, Chaejoon

doi:10.1016/j.febslet.2004.03.062

Cited by 53 publications

(85 citation statements)

References 29 publications

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“…These observations further supports the idea that the cradle-like and ordered conformation of the active site loop observed in the X-ray structure is due to ligand binding [7]. The mobility of the active site loops as an important structure feature in ligand binding has been revealed in many phosphatases, such as low molecular weight protein tyrosine phosphatase from Bos taurus (PDB 1BVH) [26], Campylobacter jejuni (2GI4) [27], Tritrichomonas foetus (1P8A) [28], B. subtilis (1ZGG) [29], E. coli (2FEK) [30], and human PRL-3 (1V3Z) [31], and human phosphohistidine phosphatase 1 (2AI6) [32], suggesting that active site conformational flexibility should be considered to understand ligand recognition and design inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Solution structure and conformational heterogeneity of acylphosphatase from Bacillus subtilis

et al. 2010

FEBS Letters

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a b s t r a c tAcylphosphatase is a small enzyme that catalyzes the hydrolysis of acyl phosphates. Here, we present the solution structure of acylphosphatase from Bacillus subtilis (BsAcP), the first from a Gram-positive bacterium. We found that its active site is disordered, whereas it converted to an ordered state upon ligand binding. The structure of BsAcP is sensitive to pH and it has multiple conformations in equilibrium at acidic pH (pH < 5.8). Only one main conformation could bind ligand, and the relative population of these states is modulated by ligand concentration. This study provides direct evidence for the role of ligand in conformational selection.

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Section: Discussionmentioning

confidence: 99%

Solution structure and conformational heterogeneity of acylphosphatase from Bacillus subtilis

et al. 2010

FEBS Letters

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“…Due to the high sequence similarity, it is expected that the PRL-3 and PRL-1 structures would have a large structural similarity. However, significant differences in the P-loop structure exist between the PRL-1 crystal structure and the PRL-3 nuclear magnetic resonance structure published by Kozlov et al The PRL-3 nuclear magnetic resonance structure P-loop [C(X) 5 Fig. 2A and B).…”

Section: Prl Three-dimensional Structures and Implications Intheir Fumentioning

confidence: 99%

“…Phosphatase of regenerating liver (PRL)-1, PRL-2, and PRL-3 collectively make up a subgroup of VH1-like PTPs (4). Based on amino acid sequence, the most closely related phosphatases outside the subgroup are dualspecificity phosphatases CDC14 (regulates mitotic exit) and PTEN (a tumor suppressor with lipid phosphatase activity), with an amino acid sequence identity of f20% and 17%, respectively (5).…”

Section: Introductionmentioning

confidence: 99%

“…The protein tyrosine phosphatase (PTP) superfamily of phosphatases, which are defined by the signature C(X) 5 R active site motif, encompasses a large group of enzymes that play key roles in the regulation of protein phosphorylation. In recent years, several PTPs have been implicated in a variety of diseases and have emerged as therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

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PRL phosphatases as potential molecular targets in cancer

Stephens¹,

Han

Gokhale

et al. 2005

Molecular Cancer Therapeutics

130

157

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The phosphatase of regenerating liver (PRL) family of phosphatases, consisting of PRL-1, PRL-2, and PRL-3, represents an intriguing group of proteins being validated as biomarkers and therapeutic targets in cancer. Individual PRLs are overexpressed in a variety of cancer cell lines and tissues when compared with their normal counterparts. More importantly, several recent studies have shown that PRL-3 is expressed at higher levels and at a greater frequency in colorectal cancer metastases compared with primary colorectal tumors and normal colon tissue. Ectopic expression of PRLs in nontumorigenic cells can influence proliferation and the migratory and invasive properties of cells, while knockdown of endogenous PRL-3 or PRL-1 in cancerous cells using small interfering RNA can abrogate cell motility and ability to metastasize in a mouse model. However, the exact biological function and cellular substrates of the PRLs remain unclear. This review will discuss what is known about the PRLs, what makes the PRLs possible attractive targets for therapeutic intervention, and the possible future directions in PRL biology and inhibitor identification. [Mol Cancer Ther 2005;4(11):1653 -61]

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“…Inhibition of PRL activity might be carried out using phosphatase inhibitors targeting the consensus phosphatase motif, farnesyltransferase inhibitors, interference RNA or monoclonal antibody as well [9,[35][36][37] . Recent progress in active recombinant PRL-3 production and findings on PRL-3 structure will undoubtedly facilitate the development of PRL-3 inhibitors [38][39][40] . Detection of PRL-3 expression would be able to provide supportive information for anti-cancer therapy.…”

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confidence: 99%

Expression of phosphatase regenerating liver 3 is an independent prognostic indicator for gastric cancer

Nakamura¹,

Lü²,

Shou³

et al. 2009

WJG

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AIM:To investigate the prognostic significance of phosphatase regenerating liver 3 (PRL-3) protein expression in gastric cancer. METHODS:PRL-3 expression in paraffin-embedded tumor specimens from 293 patients with gastric cancer was studied retrospectively by immunohistochemistry. Monoclonal antibody specifically against PRL-3, 3B6, was obtained with hybridoma technique. RESULTS:Positive PRL-3 expression was detected in 43.3% (127 of 293) of gastric cancer cases. High expression of PRL-3 was positively correlated with tumor size, depth of invasion, vascular/lymphatic invasion, lymph node metastasis, high TNM stage and tumor recurrence. Patients with positive PRL-3 expression had a significantly lower 5-year survival rate than those with negative expression (28.3% vs 51.9%, P < 0.0001). Patients who received curative surgery, and with positive PRL-3 expression had a significant shorter overall survival and disease-free disadvantage over patients with negative expression (hazard ratio of 16.7 and 16.6, respectively; P < 0.0001 for both).Multivariate analysis revealed that PRL-3 expression was an independent prognostic indicator for overall and disease-free survival of gastric cancer patients, particularly for survival in TNM stage Ⅲ patients.CONCLUSION: PRL-3 expression is a new independent prognostic indicator to predict the potential of recurrence and survival in patients with gastric cancer at the time of tumor resection.

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Structure of human PRL‐3, the phosphatase associated with cancer metastasis

Cited by 53 publications

References 29 publications

Solution structure and conformational heterogeneity of acylphosphatase from Bacillus subtilis

Solution structure and conformational heterogeneity of acylphosphatase from Bacillus subtilis

PRL phosphatases as potential molecular targets in cancer

Expression of phosphatase regenerating liver 3 is an independent prognostic indicator for gastric cancer

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