Trimeric Structure of PRL-1 Phosphatase Reveals an Active Enzyme Conformation and Regulation Mechanisms

Jeong, Dae Gwin; Kim, Seung Jun; Kim, Jae-Hoon; Son, Jeong Hee; Park, Mi Rim; Lim, Sungsu; Yoon, Tae Sung; Ryu, Seong Eon

doi:10.1016/j.jmb.2004.10.061

Cited by 75 publications

(124 citation statements)

References 36 publications

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“…The resonance assignments of PRL-1 and PRL-2 have also been reported (6,14). More recently, the crystal structure of PRL-1 has been determined at 2.7-Å resolution (12). Due to the high sequence similarity, it is expected that the PRL-3 and PRL-1 structures would have a large structural similarity.…”

Section: Prl Three-dimensional Structures and Implications Intheir Fumentioning

confidence: 80%

“…It is interesting, however, that PRL-1 was not found overexpressed in cancerous cell lines derived from brain or colon (9). This result is rather intriguing because of the previously described close correlation between PRL-3 expression and colorectal cancer invasion and metastasis as well as PRL-1 being expressed normally (12,15,16); PRL-3 (A) is a nuclear magnetic resonance solution structure (7). in brain and differentiated colon tissue.…”

Section: Prl Expressionmentioning

confidence: 88%

“…Structural studies have shown that under oxidizing conditions a disulfide bond can form between the two residues (7,12). Therefore, the activity of PRLs might be regulated by redox status.…”

Section: Prl Genes and Protein Productsmentioning

confidence: 99%

“…Sequence alignments suggest that CDC14 is the closest homologue but PRL-1 and PRL-3 show the closest structural similarity to phosphatases VHR, PTEN, MKP, and KAP (7,12). However, the P-loop and active site constitution of the PRLs is significantly different from the related phosphatases PTEN (15) and VHR (ref.…”

Section: Prl Three-dimensional Structures and Implications Intheir Fumentioning

confidence: 99%

“…However, it remains unclear if, in general, PRL protein localization correlates with the level of differentiation of a cell. Recently, Jeong et al (12) presented evidence suggesting that PRL-1 might form trimers in cells. Because farnesylation alone is often insufficient for the translocation of the protein to the plasma membrane, it is possible that three farnesyl groups in the trimeric PRL-1 may provide strong adhering forces to the membrane, stabilizing the membrane association.…”

Section: Biological Functions Of Prlsmentioning

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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Section: Prl Three-dimensional Structures and Implications Intheir Fumentioning

confidence: 80%

Section: Prl Expressionmentioning

confidence: 88%

Section: Prl Genes and Protein Productsmentioning

confidence: 99%

Section: Prl Three-dimensional Structures and Implications Intheir Fumentioning

confidence: 99%

Section: Biological Functions Of Prlsmentioning

confidence: 99%

See 3 more Smart Citations

PRL phosphatases as potential molecular targets in cancer

Stephens¹,

Han

Gokhale

et al. 2005

Molecular Cancer Therapeutics

130

157

View full text Add to dashboard Cite

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Fundamental Structures and Behaviors of Proteins

Laurence

Middaugh

2010

Aggregation of Therapeutic Proteins

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PRL‐3 phosphatase and cancer metastasis

Al-Aidaroos

Zeng

2010

J of Cellular Biochemistry

110

157

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The deregulated expression of members of the phosphatase of regenerating liver (PRL) family has been implicated in the metastatic progression of multiple human cancers. Importantly, PRL-1 and PRL-3 both possess the capacity to drive key steps in metastatic progression. Yet, little is known about the regulation and oncogenic mechanisms of this emerging class of dual-specificity phosphatases. This prospect article details the involvement of PRLs in the metastatic cascade, the regulatory mechanisms controlling PRL expression, and recent efforts in the characterization of PRL-modulated pathways and substrates using biochemical and high-throughput approaches. Current advances and future prospects in anti-cancer therapy targeting this family are also discussed.

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Trimeric Structure of PRL-1 Phosphatase Reveals an Active Enzyme Conformation and Regulation Mechanisms

Cited by 75 publications

References 36 publications

PRL phosphatases as potential molecular targets in cancer

PRL phosphatases as potential molecular targets in cancer

Fundamental Structures and Behaviors of Proteins

PRL‐3 phosphatase and cancer metastasis

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